{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:04:37Z","timestamp":1791212677530,"version":"4.1.0"},"reference-count":213,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS088645"],"award-info":[{"award-number":["NS088645"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitochondria plays privotal role in diverse pathways that regulate cellular function and survival, and have emerged as a prime focus in aging and age-associated motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Accumulating evidence suggests that many amyloidogenic proteins, including MND-associated RNA\/DNA-binding proteins fused in sarcoma (FUS) and TAR DNA binding protein (TDP)-43, are strongly linked to mitochondrial dysfunction. Animal model and patient studies have highlighted changes in mitochondrial structure, plasticity, replication\/copy number, mitochondrial DNA instability, and altered membrane potential in several subsets of MNDs, and these observations are consistent with the evidence of increased excitotoxicity, induction of reactive oxygen species, and activation of intrinsic apoptotic pathways. Studies in MND rodent models also indicate that mitochondrial abnormalities begin prior to the clinical and pathological onset of the disease, suggesting a causal role of mitochondrial dysfunction. Our recent studies, which demonstrated the involvement of specific defects in DNA break-ligation mediated by DNA ligase 3 (LIG3) in FUS-associated ALS, raised a key question of its potential implication in mitochondrial DNA transactions because LIG3 is essential for both mitochondrial DNA replication and repair. This question, as well as how wild-type and mutant MND-associated factors affect mitochondria, remain to be elucidated. These new investigation avenues into the mechanistic role of mitochondrial dysfunction in MNDs are critical to identify therapeutic targets to alleviate mitochondrial toxicity and its consequences. In this article, we critically review recent advances in our understanding of mitochondrial dysfunction in diverse subgroups of MNDs and discuss challenges and future directions.<\/jats:p>","DOI":"10.3390\/cells9041065","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T11:42:14Z","timestamp":1587728534000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Altered Mitochondrial Dynamics in Motor Neuron Disease: An Emerging Perspective"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-7351","authenticated-orcid":false,"given":"Manohar","family":"Kodavati","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7333-8123","authenticated-orcid":false,"given":"Muralidhar L.","family":"Hegde","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Neurosurgery, Weill Medical College, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrneurol.2011.152","article-title":"Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis","volume":"7","author":"Ferraiuolo","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","unstructured":"GBD 2016 Motor Neuron Disease Collaborators (2018). Global, regional, and national burden of motor neuron diseases 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 17, 1083\u20131097."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/WCO.0b013e32832ffbe3","article-title":"Recent advances in motor neuron disease","volume":"22","author":"Robberecht","year":"2009","journal-title":"Curr. Opin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/17482960802645008","article-title":"The cognitive profile of amyotrophic lateral sclerosis: A meta-analysis","volume":"11","author":"Raaphorst","year":"2010","journal-title":"Amyotroph. Lateral Scler"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1212\/01.WNL.0000055861.95202.8D","article-title":"Are amyotrophic lateral sclerosis patients cognitively normal?","volume":"60","author":"Murphy","year":"2003","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.brainres.2014.09.041","article-title":"Biomarker development for C9orf72 repeat expansion in ALS","volume":"1607","author":"Mendez","year":"2015","journal-title":"Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3109\/17482961003610853","article-title":"The sex ratio in amyotrophic lateral sclerosis: A population based study","volume":"11","author":"Manjaly","year":"2010","journal-title":"Amyotroph. Lateral Scler"},{"key":"ref_8","first-page":"137","article-title":"Presenile dementia with motor neuron disease","volume":"4","author":"Mitsuyama","year":"1993","journal-title":"Dementia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/brain\/104.2.217","article-title":"Amyotrophic lateral sclerosis and its association with dementia, parkinsonism and other neurological disorders: A review","volume":"104","author":"Hudson","year":"1981","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"806306","DOI":"10.1155\/2012\/806306","article-title":"ALS and Frontotemporal Dysfunction: A Review","volume":"2012","author":"Achi","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/ana.100","article-title":"Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Kii Peninsula of Japan: Clinical and neuropathological study and tau analysis","volume":"49","author":"Kuzuhara","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1093\/aje\/kwh179","article-title":"Prospective study of cigarette smoking and amyotrophic lateral sclerosis","volume":"160","author":"Weisskopf","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/JOM.0b013e31827f37f8","article-title":"Occupational exposure to extremely low-frequency magnetic fields and neurodegenerative disease: A meta-analysis","volume":"55","author":"Vergara","year":"2013","journal-title":"J. Occup. Environ. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1289\/ehp.6109","article-title":"Amyotrophic lateral sclerosis, lead, and genetic susceptibility: Polymorphisms in the delta-aminolevulinic acid dehydratase and vitamin D receptor genes","volume":"111","author":"Kamel","year":"2003","journal-title":"Environ. Health Perspect"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1136\/jnnp.2010.218982","article-title":"Physical fitness, but not muscle strength, is a risk factor for death in amyotrophic lateral sclerosis at an early age","volume":"83","author":"Mattsson","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/EDE.0b013e3181632c5d","article-title":"Diet and amyotrophic lateral sclerosis","volume":"19","author":"Morozova","year":"2008","journal-title":"Epidemiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1212\/WNL.54.1.20","article-title":"Detection and cellular localization of enterovirus RNA sequences in spinal cord of patients with ALS","volume":"54","author":"Berger","year":"2000","journal-title":"Neurology"},{"key":"ref_18","first-page":"744","article-title":"Deux cas d\u2019atrophie musculaire progressive avec lesions de la substance grise et des faisceaux anterolateraux de la moelle epiniere","volume":"2","author":"Charcot","year":"1869","journal-title":"Archives Pathologie Normale Pathologique"},{"key":"ref_19","first-page":"cer-05-17","article-title":"Genetics and ALS: Cause for Optimism","volume":"2017","author":"Pochet","year":"2017","journal-title":"Cerebrum"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1002\/humu.22157","article-title":"ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics","volume":"33","author":"Abel","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3109\/17482968.2011.584629","article-title":"Keeping up with genetic discoveries in amyotrophic lateral sclerosis: The ALSoD and ALSGene databases","volume":"12","author":"Lill","year":"2011","journal-title":"Amyotroph. Lateral Scler"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/WCO.0b013e32835a3efb","article-title":"How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and frontotemporal dementia: Can we learn from other noncoding repeat expansion disorders?","volume":"25","author":"Rademakers","year":"2012","journal-title":"Curr. Opin. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1474-4422(12)70043-1","article-title":"Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: A cross-sectional study","volume":"11","author":"Majounie","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/humu.22244","article-title":"A pan-European study of the C9orf72 repeat associated with FTLD: Geographic prevalence, genomic instability, and intermediate repeats","volume":"34","author":"Gijselinck","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1046\/j.1471-4159.1998.70020715.x","article-title":"CuZn-superoxide dismutase, extracellular superoxide dismutase, and glutathione peroxidase in blood from individuals homozygous for Asp90Ala CuZu-superoxide dismutase mutation","volume":"70","author":"Andersen","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1126\/science.281.5384.1851","article-title":"Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1","volume":"281","author":"Bruijn","year":"1998","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14157","DOI":"10.1073\/pnas.0700477104","article-title":"Soluble misfolded subfractions of mutant superoxide dismutase-1s are enriched in spinal cords throughout life in murine ALS models","volume":"104","author":"Zetterstrom","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1126\/science.1166066","article-title":"Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis","volume":"323","author":"Kwiatkowski","year":"2009","journal-title":"Science"},{"key":"ref_30","first-page":"765","article-title":"FUS mutations in frontotemporal lobar degeneration with amyotrophic lateral sclerosis","volume":"22","author":"Broustal","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1038\/s41467-018-06111-6","article-title":"Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, H., and Hegde, M.L. (2019). New Mechanisms of DNA Repair Defects in Fused in Sarcoma-Associated Neurodegeneration: Stage Set for DNA Repair-Based Therapeutics?. J. Exp. Neurosci., 13.","DOI":"10.1177\/1179069519856358"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sama, R.R., Ward, C.L., and Bosco, D.A. (2014). Functions of FUS\/TLS from DNA repair to stress response: Implications for ALS. ASN Neuro, 6.","DOI":"10.1177\/1759091414544472"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-009-0612-2","article-title":"Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: An update","volume":"119","author":"Mackenzie","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R46","DOI":"10.1093\/hmg\/ddq137","article-title":"TDP-43 and FUS\/TLS: Emerging roles in RNA processing and neurodegeneration","volume":"19","author":"Polymenidou","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1750-1326-8-28","article-title":"Genetics of amyotrophic lateral sclerosis: An update","volume":"8","author":"Chen","year":"2013","journal-title":"Mol. Neurodegener"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/2045125317739818","article-title":"Frontotemporal dementia: Latest evidence and clinical implications","volume":"8","author":"Young","year":"2018","journal-title":"Adv. Psychopharmacol"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s12031-011-9593-4","article-title":"Pathogenesis of the tauopathies","volume":"45","author":"Goedert","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S1474-4422(08)70194-7","article-title":"Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia","volume":"7","author":"Heutink","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1093\/hmg\/ddl241","article-title":"Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration","volume":"15","author":"Gass","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jns.2008.08.024","article-title":"Progranulin (PGRN) expression in ALS: An immunohistochemical study","volume":"276","author":"Irwin","year":"2009","journal-title":"J. Neurol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1097\/NEN.0b013e3181fc9aea","article-title":"Microglial upregulation of progranulin as a marker of motor neuron degeneration","volume":"69","author":"Philips","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/path.2580","article-title":"Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse models","volume":"219","author":"Pereson","year":"2009","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-genom-082509-141720","article-title":"The mitochondrial proteome and human disease","volume":"11","author":"Calvo","year":"2010","journal-title":"Annu Rev. Genom. Hum. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1093\/molbev\/msp068","article-title":"A proteomic survey of Chlamydomonas reinhardtii mitochondria sheds new light on the metabolic plasticity of the organelle and on the nature of the alpha-proteobacterial mitochondrial ancestor","volume":"26","author":"Atteia","year":"2009","journal-title":"Mol. Biol. Evol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.tibs.2011.01.004","article-title":"Mitochondrial protein quality control during biogenesis and aging","volume":"36","author":"Baker","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.ceb.2011.05.007","article-title":"Regulating mitochondrial outer membrane proteins by ubiquitination and proteasomal degradation","volume":"23","author":"Karbowski","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and selective fusion govern mitochondrial segregation and elimination by autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1016\/j.biocel.2009.04.003","article-title":"Structural and functional organization of the mitochondrial respiratory chain: A dynamic super-assembly","volume":"41","author":"Lenaz","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"D1251","DOI":"10.1093\/nar\/gkv1003","article-title":"MitoCarta2.0: An updated inventory of mammalian mitochondrial proteins","volume":"44","author":"Calvo","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-biochem-060815-014402","article-title":"Maintenance and Expression of Mammalian Mitochondrial DNA","volume":"85","author":"Gustafsson","year":"2016","journal-title":"Annu. Rev. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11288","DOI":"10.1073\/pnas.1512131112","article-title":"Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid","volume":"112","author":"Kukat","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00424-012-1112-0","article-title":"Mitochondria, calcium-dependent neuronal death and neurodegenerative disease","volume":"464","author":"Duchen","year":"2012","journal-title":"Pfl\u00fcgers Archiv"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1254\/jphs.CPJ04006X","article-title":"Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer\u2019s disease","volume":"97","author":"Takuma","year":"2005","journal-title":"J. Pharm. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1161\/01.STR.0000256294.46009.29","article-title":"Ca2+ signals and neuronal death in brain ischemia","volume":"38","author":"Bano","year":"2007","journal-title":"Stroke"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1474-9726.2007.00296.x","article-title":"The importance of being subtle: Small changes in calcium homeostasis control cognitive decline in normal aging","volume":"6","author":"Toescu","year":"2007","journal-title":"Aging Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.cell.2013.12.042","article-title":"Activity-driven local ATP synthesis is required for synaptic function","volume":"156","author":"Rangaraju","year":"2014","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/BF01218351","article-title":"Axoplasmic organelles at nodes of Ranvier. I. Occurrence and distribution in large myelinated spinal root axons of the adult cat","volume":"22","author":"Berthold","year":"1993","journal-title":"J. Neurocytol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1042\/EBC20170104","article-title":"Mitochondrial dynamics: Overview of molecular mechanisms","volume":"62","author":"Tilokani","year":"2018","journal-title":"Essays Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.bbadis.2011.10.011","article-title":"Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer\u2019s disease: Implications to mitochondria-targeted antioxidant therapeutics","volume":"1822","author":"Reddy","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-physiol-020518-114358","article-title":"Evolving Concepts of Mitochondrial Dynamics","volume":"81","author":"Dorn","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development","volume":"160","author":"Chen","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cell.2007.06.026","article-title":"Mitochondrial fusion protects against neurodegeneration in the cerebellum","volume":"130","author":"Chen","year":"2007","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1101\/gad.1658508","article-title":"Mitochondrial dynamics and apoptosis","volume":"22","author":"Suen","year":"2008","journal-title":"Genes Dev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"31462","DOI":"10.1038\/srep31462","article-title":"Mfn2 is Required for Mitochondrial Development and Synapse Formation in Human Induced Pluripotent Stem Cells\/hiPSC Derived Cortical Neurons","volume":"6","author":"Fang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/jmedgenet-2015-103361","article-title":"Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation","volume":"53","author":"Spiegel","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1056\/NEJMoa064436","article-title":"A lethal defect of mitochondrial and peroxisomal fission","volume":"356","author":"Waterham","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.stem.2016.04.015","article-title":"Mitochondrial Dynamics Impacts Stem Cell Identity and Fate Decisions by Regulating a Nuclear Transcriptional Program","volume":"19","author":"Khacho","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.neuron.2016.12.017","article-title":"Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis","volume":"93","author":"Beckervordersandforth","year":"2017","journal-title":"Neuron"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1242\/jcs.104.3.917","article-title":"The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth","volume":"104","author":"Morris","year":"1993","journal-title":"J. Cell Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7888","DOI":"10.1073\/pnas.1205869109","article-title":"Calpain cleaves and activates the TRPC5 channel to participate in semaphorin 3A-induced neuronal growth cone collapse","volume":"109","author":"Kaczmarek","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/cdd.2008.57","article-title":"Mitochondrial fission and fusion dynamics: The long and short of it","volume":"15","author":"Berman","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20150","DOI":"10.1074\/jbc.273.32.20150","article-title":"Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae","volume":"273","author":"Rapaport","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/90116","article-title":"Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria","volume":"28","author":"Ono","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.tox.2017.07.019","article-title":"Mitochondrial fusion, fission, and mitochondrial toxicity","volume":"391","author":"Meyer","year":"2017","journal-title":"Toxicology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1523\/JNEUROSCI.2799-15.2016","article-title":"Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons","volume":"36","author":"Morsci","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1091\/mbc.e05-06-0526","article-title":"Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons","volume":"17","author":"Pilling","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0304-4165(96)00053-0","article-title":"The effects of temperature, pH, and magnesium on the diffusion coefficient of ATP in solutions of physiological ionic strength","volume":"1291","author":"Hubley","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1083\/jcb.200406038","article-title":"Control of mitochondrial motility and distribution by the calcium signal: A homeostatic circuit","volume":"167","author":"Yi","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cell.2007.11.024","article-title":"Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation","volume":"132","author":"Kang","year":"2008","journal-title":"Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1126\/science.285.5435.1870","article-title":"Long-term potentiation\u2014A decade of progress?","volume":"285","author":"Malenka","year":"1999","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0006-291X(03)00627-2","article-title":"Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death","volume":"304","author":"Mattson","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0006-8993(82)90456-5","article-title":"Changes in the hippocampal slices energy metabolism following stimulation and long-term potentiation of Schaffer collaterals-pyramidal cell synapses tested with the 2-deoxyglucose technique","volume":"237","author":"Wieraszko","year":"1982","journal-title":"Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0006-8993(86)90130-7","article-title":"Hippocampal long-term potentiation increases mitochondrial calcium pump activity in rat","volume":"382","author":"Stanton","year":"1986","journal-title":"Brain Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0169-328X(98)00165-X","article-title":"Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus","volume":"60","author":"Williams","year":"1998","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1113\/jphysiol.1975.sp010974","article-title":"On the role of mitochondria in transmitter release from motor nerve terminals","volume":"248","author":"Alnaes","year":"1975","journal-title":"J. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/(SICI)1097-4547(19990401)56:1<8::AID-JNR2>3.0.CO;2-G","article-title":"Evidence for mitochondrial control of neuronal polarity","volume":"56","author":"Mattson","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41598-017-00676-w","article-title":"Messenger RNAs localized to distal projections of human stem cell derived neurons","volume":"7","author":"Bigler","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sahoo, P.K., Smith, D.S., Perrone-Bizzozero, N., and Twiss, J.L. (2018). Axonal mRNA transport and translation at a glance. J. Cell Sci., 131.","DOI":"10.1242\/jcs.196808"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.mcn.2010.01.009","article-title":"Regulation of axonal trafficking of cytochrome c oxidase IV mRNA","volume":"43","author":"Aschrafi","year":"2010","journal-title":"Mol. Cell Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1002\/mds.25135","article-title":"Living on the edge with too many mouths to feed: Why dopamine neurons die","volume":"27","author":"Bolam","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"8300","DOI":"10.1523\/JNEUROSCI.18-20-08300.1998","article-title":"Three-dimensional structure and composition of CA3\u2192CA1 axons in rat hippocampal slices: Implications for presynaptic connectivity and compartmentalization","volume":"18","author":"Shepherd","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.neuron.2017.09.055","article-title":"Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture","volume":"96","author":"Misgeld","year":"2017","journal-title":"Neuron"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1242\/jcs.109.5.971","article-title":"Organelle motility and metabolism in axons vs dendrites of cultured hippocampal neurons","volume":"109","author":"Overly","year":"1996","journal-title":"J. Cell Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/1096-9861(20001120)427:3<340::AID-CNE2>3.0.CO;2-Y","article-title":"Movement of mitochondria in the axons and dendrites of cultured hippocampal neurons","volume":"427","author":"Ligon","year":"2000","journal-title":"J. Comp. Neurol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/j.1471-4159.1992.tb09439.x","article-title":"Brain cytochrome oxidase in Alzheimer\u2019s disease","volume":"59","author":"Kish","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0197-4580(01)00314-1","article-title":"Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer\u2019s disease","volume":"23","author":"Bosetti","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.brainresrev.2010.11.004","article-title":"Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases","volume":"67","author":"Reddy","year":"2011","journal-title":"Brain Res. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-94-007-2869-1_12","article-title":"Mitochondria in neurodegeneration","volume":"942","author":"Lezi","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.cell.2011.10.018","article-title":"PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility","volume":"147","author":"Wang","year":"2011","journal-title":"Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1023\/B:NERE.0000014824.04728.dd","article-title":"The energetics of Huntington\u2019s disease","volume":"29","author":"Browne","year":"2004","journal-title":"Neurochem. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.neulet.2012.10.003","article-title":"Full-length TDP-43 and its C-terminal fragments activate mitophagy in NSC34 cell line","volume":"530","author":"Hong","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"10769","DOI":"10.1074\/jbc.M113.515940","article-title":"Mitochondrial dysfunction and decrease in body weight of a transgenic knock-in mouse model for TDP-43","volume":"289","author":"Stribl","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/sj.embor.7401062","article-title":"Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death","volume":"8","author":"Cribbs","year":"2007","journal-title":"EMBO Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","article-title":"The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons","volume":"22","author":"Wang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neulet.2018.04.053","article-title":"TDP-43 interacts with mitochondrial proteins critical for mitophagy and mitochondrial dynamics","volume":"678","author":"Davis","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nm.4130","article-title":"The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity","volume":"22","author":"Wang","year":"2016","journal-title":"Nat. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-017-0180-1","article-title":"Mutant TDP-43 does not impair mitochondrial bioenergetics in vitro and in vivo","volume":"12","author":"Kawamata","year":"2017","journal-title":"Mol. Neurodegener"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, P., Deng, J., Dong, J., Liu, J., Bigio, E.H., Mesulam, M., Wang, T., Sun, L., Wang, L., and Lee, A.Y. (2019). TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1007947"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1038\/ncomms4996","article-title":"ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS\/FTD-associated TDP-43","volume":"5","author":"Stoica","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.bbabio.2009.01.019","article-title":"Mitochondrial calcium as a key regulator of mitochondrial ATP production in mammalian cells","volume":"1787","author":"Griffiths","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"aaf5549","DOI":"10.1126\/science.aaf5549","article-title":"ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells","volume":"353","author":"Lewis","year":"2016","journal-title":"Science"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"132933","DOI":"10.1016\/j.neulet.2017.06.052","article-title":"The role of mitochondria in amyotrophic lateral sclerosis","volume":"710","author":"Smith","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1111\/j.1750-3639.2010.00413.x","article-title":"Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions","volume":"20","author":"Huang","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/hmg\/ddr448","article-title":"Arginine methylation by PRMT1 regulates nuclear-cytoplasmic localization and toxicity of FUS\/TLS harbouring ALS-linked mutations","volume":"21","author":"Tradewell","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41467-017-00911-y","article-title":"HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients","volume":"8","author":"Guo","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Deng, J., Yang, M., Chen, Y., Chen, X., Liu, J., Sun, S., Cheng, H., Li, Y., Bigio, E.H., and Mesulam, M. (2015). FUS Interacts with HSP60 to Promote Mitochondrial Damage. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005357"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"E9678","DOI":"10.1073\/pnas.1806655115","article-title":"FUS interacts with ATP synthase beta subunit and induces mitochondrial unfolded protein response in cellular and animal models","volume":"115","author":"Deng","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.15252\/embr.201541726","article-title":"ALS\/FTD-associated FUS activates GSK-3beta to disrupt the VAPB-PTPIP51 interaction and ER-mitochondria associations","volume":"17","author":"Stoica","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1093\/hmg\/ddm226","article-title":"Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content","volume":"16","author":"Chapman","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4668","DOI":"10.1093\/hmg\/ddx348","article-title":"Amyotrophic lateral sclerosis-associated mutant SOD1 inhibits anterograde axonal transport of mitochondria by reducing Miro1 levels","volume":"26","author":"Moller","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2174\/15672026113109990060","article-title":"Mitochondrial fusion and fission proteins expression dynamically change in a murine model of amyotrophic lateral sclerosis","volume":"10","author":"Liu","year":"2013","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2004.06.021","article-title":"Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria","volume":"43","author":"Pasinelli","year":"2004","journal-title":"Neuron"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1093\/brain\/awf167","article-title":"Mitochondrial dysfunction in a cell culture model of familial amyotrophic lateral sclerosis","volume":"125","author":"Menzies","year":"2002","journal-title":"Brain"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/j.1471-4159.2006.03619.x","article-title":"Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu\/Zn-superoxide dismutase mutant mice","volume":"96","author":"Damiano","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1093\/hmg\/ddr381","article-title":"Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer\u2019s disease","volume":"20","author":"Calkins","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40478-016-0316-5","article-title":"Gene-specific mitochondria dysfunctions in human TARDBP and C9ORF72 fibroblasts","volume":"4","author":"Onesto","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72-Related ALS\/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons","volume":"92","author":"Lu","year":"2016","journal-title":"Neuron"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/stem.2388","article-title":"C9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia","volume":"34","author":"Dafinca","year":"2016","journal-title":"Stem Cells"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.aquatox.2009.08.003","article-title":"Effects of benzo[a]pyrene on mitochondrial and nuclear DNA damage in Atlantic killifish (Fundulus heteroclitus) from a creosote-contaminated and reference site","volume":"95","author":"Jung","year":"2009","journal-title":"Aquat. Toxicol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/j.1460-2075.1982.tb01149.x","article-title":"Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction","volume":"1","author":"Rydberg","year":"1982","journal-title":"EMBO J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1006\/abbi.1997.0167","article-title":"Transport of S-adenosylmethionine in isolated rat liver mitochondria","volume":"343","author":"Horne","year":"1997","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.mad.2008.03.002","article-title":"Mitochondrial DNA repair in aging and disease","volume":"129","author":"Druzhyna","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.3233\/JAD-190048","article-title":"Molecular Basis of Alzheimer\u2019s Disease: Focus on Mitochondria","volume":"72","author":"Oliver","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/362709a0","article-title":"Instability and decay of the primary structure of DNA","volume":"362","author":"Lindahl","year":"1993","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbamcr.2010.10.002","article-title":"DNA repair in organelles: Pathways, organization, regulation, relevance in disease and aging","volume":"1813","author":"Boesch","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.semcdb.2011.10.007","article-title":"DNA double-strand break repair pathways, chromosomal rearrangements and cancer","volume":"22","author":"Kasparek","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1042\/BST20160162","article-title":"Mitochondrial DNA replication: A PrimPol perspective","volume":"45","author":"Bailey","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"26349","DOI":"10.1074\/jbc.M803491200","article-title":"Long patch base excision repair in mammalian mitochondrial genomes","volume":"283","author":"Szczesny","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1021\/cr040463d","article-title":"DNA polymerase gamma in mitochondrial DNA replication and repair","volume":"106","author":"Graziewicz","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1093\/nar\/27.4.1198","article-title":"Double strand break rejoining by mammalian mitochondrial extracts","volume":"27","author":"Lakshmipathy","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"27536","DOI":"10.1074\/jbc.271.44.27536","article-title":"Mammalian mitochondria possess homologous DNA recombination activity","volume":"271","author":"Thyagarajan","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1093\/nar\/27.16.3348","article-title":"Mammalian mitochondrial extracts possess DNA end-binding activity","volume":"27","author":"Coffey","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1091\/mbc.e15-05-0260","article-title":"Microhomology-mediated end joining is the principal mediator of double-strand break repair during mitochondrial DNA lesions","volume":"27","author":"Tadi","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1093\/nar\/gkp348","article-title":"Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks","volume":"37","author":"Bacman","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1084\/jem.20091834","article-title":"Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging","volume":"207","author":"Kamenisch","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.cell.2016.04.006","article-title":"Fanconi Anemia Proteins Function in Mitophagy and Immunity","volume":"165","author":"Sumpter","year":"2016","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"4696","DOI":"10.1073\/pnas.1818415116","article-title":"Motor neuron disease-associated loss of nuclear TDP-43 is linked to DNA double-strand break repair defects","volume":"116","author":"Mitra","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nature09794","article-title":"Crucial role for DNA ligase III in mitochondria but not in Xrcc1-dependent repair","volume":"471","author":"Simsek","year":"2011","journal-title":"Nature"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nchembio.2102","article-title":"Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes","volume":"12","author":"Wisnovsky","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0921-8777(00)00068-9","article-title":"Mitochondrial localization of APE\/Ref-1 in thyroid cells","volume":"485","author":"Tell","year":"2001","journal-title":"Mutat. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1093\/nar\/29.11.2349","article-title":"Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen","volume":"29","author":"Tsuchimoto","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"7437","DOI":"10.1073\/pnas.1100084108","article-title":"Aprataxin localizes to mitochondria and preserves mitochondrial function","volume":"108","author":"Sykora","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.molcel.2008.09.024","article-title":"Human DNA2 is a mitochondrial nuclease\/helicase for efficient processing of DNA replication and repair intermediates","volume":"32","author":"Zheng","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.dnarep.2009.07.008","article-title":"Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity","volume":"8","author":"Kalifa","year":"2009","journal-title":"DNA Repair"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.dnarep.2012.11.009","article-title":"Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB)","volume":"12","author":"Samson","year":"2013","journal-title":"DNA Repair"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1093\/nar\/28.6.1355","article-title":"Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria","volume":"28","author":"Ohtsubo","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1073\/pnas.0507444103","article-title":"The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase","volume":"103","author":"Vartanian","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1074\/jbc.M111.272179","article-title":"Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3\u2032-phosphatase in maintenance of mitochondrial genome","volume":"287","author":"Mandal","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0921-8777(00)00015-X","article-title":"Cell-cycle regulation, intracellular sorting and induced overexpression of the human NTH1 DNA glycosylase involved in removal of formamidopyrimidine residues from DNA","volume":"460","author":"Luna","year":"2000","journal-title":"Mutat. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"14659","DOI":"10.1074\/jbc.270.24.14659","article-title":"Intracellular localization of 8-oxo-dGTPase in human cells, with special reference to the role of the enzyme in mitochondria","volume":"270","author":"Kang","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1091\/mbc.10.5.1637","article-title":"Expression and differential intracellular localization of two major forms of human 8-oxoguanine DNA glycosylase encoded by alternatively spliced OGG1 mRNAs","volume":"10","author":"Nishioka","year":"1999","journal-title":"Mol. Biol. Cell"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"31616","DOI":"10.1074\/jbc.M109.025882","article-title":"Mitochondrial localization of PARP-1 requires interaction with mitofilin and is involved in the maintenance of mitochondrial DNA integrity","volume":"284","author":"Rossi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Sykora, P., Kanno, S., Akbari, M., Kulikowicz, T., Baptiste, B.A., Leandro, G.S., Lu, H., Tian, J., May, A., and Becker, K.A. (2017). DNA Polymerase Beta Participates in Mitochondrial DNA Repair. Mol. Cell Biol., 37.","DOI":"10.1128\/MCB.00237-17"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5835","DOI":"10.1016\/S0021-9258(18)42629-4","article-title":"Purification and identification of subunit structure of the human mitochondrial DNA polymerase","volume":"267","author":"Gray","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"19790","DOI":"10.1073\/pnas.1009814107","article-title":"Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria","volume":"107","author":"Das","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/nar\/25.4.750","article-title":"Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene","volume":"25","author":"Nilsen","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Singh, B., Li, X., Owens, K.M., Vanniarajan, A., Liang, P., and Singh, K.K. (2015). Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140409"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1007\/s00018-017-2702-y","article-title":"Homologous recombination-mediated repair of DNA double-strand breaks operates in mammalian mitochondria","volume":"75","author":"Dahal","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"18984","DOI":"10.1074\/jbc.M109.099846","article-title":"Discovery of a novel function for human Rad51: Maintenance of the mitochondrial genome","volume":"285","author":"Sage","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"R632","DOI":"10.1152\/ajpregu.00853.2010","article-title":"Mre11 is expressed in mammalian mitochondria where it binds to mitochondrial DNA","volume":"301","author":"Dmitrieva","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1093\/hmg\/ddm166","article-title":"Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells","volume":"16","author":"Ambrose","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.molcel.2015.08.008","article-title":"ATR Plays a Direct Antiapoptotic Role at Mitochondria, which Is Regulated by Prolyl Isomerase Pin1","volume":"60","author":"Hilton","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1093\/nar\/28.19.3793","article-title":"An alternate form of Ku80 is required for DNA end-binding activity in mammalian mitochondria","volume":"28","author":"Coffey","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cellbi.2007.08.031","article-title":"Mitochondrial localization of non-histone protein HMGB1 during human endothelial cell-Toxoplasma gondii infection","volume":"32","author":"Stumbo","year":"2008","journal-title":"Cell Biol. Int."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/s41419-019-2018-y","article-title":"MLH1 deficiency leads to deregulated mitochondrial metabolism","volume":"10","author":"Rashid","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.dnarep.2009.01.021","article-title":"Novel DNA mismatch-repair activity involving YB-1 in human mitochondria","volume":"8","author":"Mason","year":"2009","journal-title":"DNA Repair"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1093\/nar\/gkv472","article-title":"XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage","volume":"43","author":"Liu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"45626","DOI":"10.1038\/srep45626","article-title":"Fancd2 in vivo interaction network reveals a non-canonical role in mitochondrial function","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1083\/jcb.200607061","article-title":"Defective mitochondrial peroxiredoxin-3 results in sensitivity to oxidative stress in Fanconi anemia","volume":"175","author":"Mukhopadhyay","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"102684","DOI":"10.1016\/j.dnarep.2019.102684","article-title":"The FANCM family Mph1 helicase localizes to the mitochondria and contributes to mtDNA stability","volume":"82","author":"Bernal","year":"2019","journal-title":"DNA Repair"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Mishra, A., Saxena, S., Kaushal, A., and Nagaraju, G. (2018). RAD51C\/XRCC3 Facilitates Mitochondrial DNA Replication and Maintains Integrity of the Mitochondrial Genome. Mol. Cell Biol., 38.","DOI":"10.1128\/MCB.00489-17"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1091\/mbc.e04-10-0895","article-title":"Phosphorylated BRCA1 is predominantly located in the nucleus and mitochondria","volume":"16","author":"Coene","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3164\/jcbn.14-42","article-title":"A mitochondrial superoxide theory for oxidative stress diseases and aging","volume":"56","author":"Indo","year":"2015","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ROS in the brain: From physiology to neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1038\/s41467-019-09566-3","article-title":"Mitochondria-specific drug release and reactive oxygen species burst induced by polyprodrug nanoreactors can enhance chemotherapy","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/347768a0","article-title":"Localization of nitric oxide synthase indicating a neural role for nitric oxide","volume":"347","author":"Bredt","year":"1990","journal-title":"Nature"},{"key":"ref_189","first-page":"111","article-title":"Localization of MAO-A and MAO-B in human brain: A step in understanding the therapeutic action of L-deprenyl","volume":"45","author":"Riederer","year":"1987","journal-title":"Adv. Neurol."},{"key":"ref_190","first-page":"23","article-title":"Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity","volume":"10","author":"Beckhauser","year":"2016","journal-title":"J. Exp. Neurosci."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jns.2007.01.039","article-title":"Vascular oxidative stress in Alzheimer disease","volume":"257","author":"Zhu","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/1873-3468.12972","article-title":"Regulation of neuronal development and function by ROS","volume":"592","author":"Oswald","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/164_2016_117","article-title":"Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function","volume":"240","author":"Indo","year":"2017","journal-title":"Handb. Exp. Pharm."},{"key":"ref_195","first-page":"12","article-title":"Selective neuronal vulnerability to oxidative stress in the brain","volume":"2","author":"Wang","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1111\/j.1471-4159.1992.tb10990.x","article-title":"Reactive oxygen species and the central nervous system","volume":"59","author":"Halliwell","year":"1992","journal-title":"J. Neurochem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"8722","DOI":"10.3390\/ijms13078722","article-title":"Mitochondrial dysfunction and oxidative stress promote apoptotic cell death in the striatum via cytochrome c\/caspase-3 signaling cascade following chronic rotenone intoxication in rats","volume":"13","author":"Lin","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1023\/B:JOBB.0000041755.22613.8d","article-title":"Deadly conversations: Nuclear-mitochondrial cross-talk","volume":"36","author":"Dawson","year":"2004","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0300-9084(02)01374-3","article-title":"Apoptosis-inducing factor (AIF): A novel caspase-independent death effector released from mitochondria","volume":"84","author":"Cande","year":"2002","journal-title":"Biochimie"},{"key":"ref_200","first-page":"120","article-title":"Alzheimer Disease and Oxidative Stress","volume":"2","author":"Perry","year":"2002","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2174\/156720511795745401","article-title":"Mitochondria as a therapeutic target for aging and neurodegenerative diseases","volume":"8","author":"Reddy","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0022-510X(00)00414-7","article-title":"Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons","volume":"180","author":"Vandenberghe","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/ana.410360608","article-title":"The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis","volume":"36","author":"Alexianu","year":"1994","journal-title":"Ann. Neurol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1365-2990.1993.tb00443.x","article-title":"Parvalbumin and calbindin D-28k in the human motor system and in motor neuron disease","volume":"19","author":"Ince","year":"1993","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.neuron.2009.02.003","article-title":"Moving or stopping mitochondria: Miro as a traffic cop by sensing calcium","volume":"61","author":"Cai","year":"2009","journal-title":"Neuron"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/j.bbamcr.2014.05.011","article-title":"At the right distance: ER-mitochondria juxtaposition in cell life and death","volume":"1843","author":"Naon","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"534705","DOI":"10.1155\/2012\/534705","article-title":"Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex","volume":"2012","author":"Deng","year":"2012","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/6568","article-title":"Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis","volume":"5","author":"Klivenyi","year":"1999","journal-title":"Nat. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1212\/01.WNL.0000142992.81995.F0","article-title":"A clinical trial of creatine in ALS","volume":"63","author":"Shefner","year":"2004","journal-title":"Neurology"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1023\/B:JOBB.0000041772.74810.92","article-title":"Mitochondrial dysfunction and oxidative damage in Alzheimer\u2019s and Parkinson\u2019s diseases and coenzyme Q10 as a potential treatment","volume":"36","author":"Beal","year":"2004","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/bs.pmbts.2016.12.010","article-title":"Mitochondria-Targeted Molecules as Potential Drugs to Treat Patients With Alzheimer\u2019s Disease","volume":"146","author":"Reddy","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Ikeda, K., and Iwasaki, Y. (2015). Edaravone, a Free Radical Scavenger, Delayed Symptomatic and Pathological Progression of Motor Neuron Disease in the Wobbler Mouse. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140316"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2006.12.015","article-title":"Lost in translation: Treatment trials in the SOD1 mouse and in human ALS","volume":"26","author":"Benatar","year":"2007","journal-title":"Neurobiol. Dis."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/1065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:27:11Z","timestamp":1760365631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/1065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,24]]},"references-count":213,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cells9041065"],"URL":"https:\/\/doi.org\/10.3390\/cells9041065","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,24]]}}}