{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:50:33Z","timestamp":1790628633671,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health-National Eye Institute","award":["EY024376"],"award-info":[{"award-number":["EY024376"]}]},{"name":"National Institutes of Health-National Eye Institute","award":["EY026930"],"award-info":[{"award-number":["EY026930"]}]},{"name":"National Institutes of Health-National Eye Institute","award":["P30EY028102"],"award-info":[{"award-number":["P30EY028102"]}]},{"name":"National Institutes of Health-National Eye Institute","award":["P30EY002520"],"award-info":[{"award-number":["P30EY002520"]}]},{"name":"National Eye Institute Vision Core Grants","award":["EY024376"],"award-info":[{"award-number":["EY024376"]}]},{"name":"National Eye Institute Vision Core Grants","award":["EY026930"],"award-info":[{"award-number":["EY026930"]}]},{"name":"National Eye Institute Vision Core Grants","award":["P30EY028102"],"award-info":[{"award-number":["P30EY028102"]}]},{"name":"National Eye Institute Vision Core Grants","award":["P30EY002520"],"award-info":[{"award-number":["P30EY002520"]}]},{"name":"Research to Prevent Blindness, Inc.","award":["EY024376"],"award-info":[{"award-number":["EY024376"]}]},{"name":"Research to Prevent Blindness, Inc.","award":["EY026930"],"award-info":[{"award-number":["EY026930"]}]},{"name":"Research to Prevent Blindness, Inc.","award":["P30EY028102"],"award-info":[{"award-number":["P30EY028102"]}]},{"name":"Research to Prevent Blindness, Inc.","award":["P30EY002520"],"award-info":[{"award-number":["P30EY002520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates. Mitochondrial dysfunction has been implicated in the pathologies of a number of degenerative retinal diseases. It is well known that photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and susceptibility to oxidative stress. However, it is unclear how defective mitochondria affect other retinal neurons. Nuclear respiratory factor 1 (Nrf1) is the major transcriptional regulator of mitochondrial biogenesis, and loss of Nrf1 leads to defective mitochondria biogenesis and eventually cell death. Here, we investigated how different retinal neurons respond to the loss of Nrf1. We provide in vivo evidence that the disruption of Nrf1-mediated mitochondrial biogenesis results in a slow, progressive degeneration of all retinal cell types examined, although they present different sensitivity to the deletion of Nrf1, which implicates differential energy demand and utilization, as well as tolerance to mitochondria defects in different neuronal cells. Furthermore, transcriptome analysis on rod-specific Nrf1 deletion uncovered a previously unknown role of Nrf1 in maintaining genome stability.<\/jats:p>","DOI":"10.3390\/cells11142203","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:17:10Z","timestamp":1657844230000},"page":"2203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Differential Susceptibility of Retinal Neurons to the Loss of Mitochondrial Biogenesis Factor Nrf1"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2561-0863","authenticated-orcid":false,"given":"Takae","family":"Kiyama","sequence":"first","affiliation":[{"name":"Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin St., MSB 7.024, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Kang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin St., MSB 7.024, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chai-An","family":"Mao","sequence":"additional","affiliation":[{"name":"Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin St., MSB 7.024, Houston, TX 77030, USA"},{"name":"The MD Anderson Cancer Center\/UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1146\/annurev.cellbio.22.010305.104638","article-title":"Mitochondrial fusion and fission in mammals","volume":"22","author":"Chan","year":"2006","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1515\/hsz-2021-0416","article-title":"Starting the engine of the powerhouse: Mitochondrial transcription and beyond","volume":"403","author":"Miranda","year":"2022","journal-title":"Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bomba-Warczak, E., and Savas, J.N. (2022). Long-lived mitochondrial proteins and why they exist. Trends Cell Biol.","DOI":"10.1016\/j.tcb.2022.02.001"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature11707","article-title":"Mitochondrial disorders as windows into an ancient organelle","volume":"491","author":"Vafai","year":"2012","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"28816","DOI":"10.1073\/pnas.2007827117","article-title":"Daily mitochondrial dynamics in cone photoreceptors","volume":"117","author":"Giarmarco","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/0748730418762152","article-title":"Circadian Regulation of Mitochondrial Dynamics in Retinal Photoreceptors","volume":"33","author":"Chang","year":"2018","journal-title":"J. Biol. Rhythm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0092-8674(00)80611-X","article-title":"Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1","volume":"98","author":"Wu","year":"1999","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1101\/gad.7.12a.2431","article-title":"NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators","volume":"7","author":"Virbasius","year":"1993","journal-title":"Genes Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev.physiol.010908.163119","article-title":"Transcriptional control of mitochondrial biogenesis and function","volume":"71","author":"Hock","year":"2009","journal-title":"Annu. Rev. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/9780470725207.ch5","article-title":"Transcriptional control of mitochondrial energy metabolism through the PGC1 coactivators","volume":"287","author":"Spiegelman","year":"2007","journal-title":"Novartis Found. Symp."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1242\/dev.112.1.335","article-title":"Gene regulatory factors of the sea urchin embryo. I. Purification by affinity chromatography and cloning of P3A2, a novel DNA-binding protein","volume":"112","author":"Calzone","year":"1991","journal-title":"Development"},{"key":"ref_12","first-page":"3641","article-title":"The Drosophila erect wing gene, which is important for both neuronal and muscle development, encodes a protein which is similar to the sea urchin P3A2 DNA binding protein","volume":"13","author":"DeSimone","year":"1993","journal-title":"Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4369","DOI":"10.1242\/dev.125.22.4369","article-title":"not really finished is crucial for development of the zebrafish outer retina and encodes a transcription factor highly homologous to human Nuclear Respiratory Factor-1 and avian Initiation Binding Repressor","volume":"125","author":"Becker","year":"1998","journal-title":"Development"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s003350010021","article-title":"Coding sequence, chromosomal localization, and expression pattern of Nrf1: The mouse homolog of Drosophila erect wing","volume":"11","author":"Schaefer","year":"2000","journal-title":"Mamm. Genome"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1101\/gad.4.6.1023","article-title":"NRF-1: A trans-activator of nuclear-encoded respiratory genes in animal cells","volume":"4","author":"Evans","year":"1990","journal-title":"Genes Dev."},{"key":"ref_16","first-page":"139","article-title":"Pathway Analysis of ChIP-Seq-Based NRF1 Target Genes Suggests a Logical Hypothesis of their Involvement in the Pathogenesis of Neurodegenerative Diseases","volume":"7","author":"Satoh","year":"2013","journal-title":"Gene Regul. Syst. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4663","DOI":"10.1016\/j.molcel.2021.09.020","article-title":"NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain","volume":"81","author":"Liu","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1038\/s41467-021-23974-4","article-title":"Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer","volume":"12","author":"Takayama","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.15252\/embj.201591437","article-title":"EglN2 associates with the NRF1-PGC1\u03b1 complex and controls mitochondrial function in breast cancer","volume":"34","author":"Zhang","year":"2015","journal-title":"EMBO J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8621","DOI":"10.1074\/jbc.M807198200","article-title":"Poly(ADP-ribose) Polymerase 1 Interacts with Nuclear Respiratory Factor 1 (NRF-1) and Plays a Role in NRF-1 Transcriptional Regulation","volume":"284","author":"Hossain","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1242\/jcs.113.23.4263","article-title":"Dynein light chain interacts with NRF-1 and EWG, structurally and functionally related transcription factors from humans and drosophila","volume":"113","author":"Herzig","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.celrep.2019.03.077","article-title":"Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse","volume":"27","author":"Kiyama","year":"2019","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.tem.2012.06.006","article-title":"Transcriptional integration of mitochondrial biogenesis","volume":"23","author":"Scarpulla","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/gene.20097","article-title":"Rhodopsin-iCre transgenic mouse line for Cre-mediated rod-specific gene targeting","volume":"41","author":"Li","year":"2005","journal-title":"Genesis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuron.2010.05.023","article-title":"Melanopsin-expressing retinal ganglion-cell photoreceptors: Cellular diversity and role in pattern vision","volume":"67","author":"Ecker","year":"2010","journal-title":"Neuron"},{"key":"ref_26","first-page":"1011","article-title":"Targeted expression of Cre recombinase to cone photoreceptors in transgenic mice","volume":"10","author":"Le","year":"2004","journal-title":"Mol. Vis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<93::AID-GENE10>3.0.CO;2-W","article-title":"Cre recombinase expression in cerebellar Purkinje cells","volume":"28","author":"Barski","year":"2000","journal-title":"Genesis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ydbio.2004.03.007","article-title":"Sonic hedgehog signaling is required for expansion of granule neuron precursors and patterning of the mouse cerebellum","volume":"270","author":"Lewis","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13024-018-0287-z","article-title":"Essential roles of mitochondrial biogenesis regulator Nrf1 in retinal development and homeostasis","volume":"13","author":"Kiyama","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S0896-6273(00)00062-3","article-title":"The murine cone photoreceptor: A single cone type expresses both S and M opsins with retinal spatial patterning","volume":"27","author":"Applebury","year":"2000","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7670","DOI":"10.1523\/JNEUROSCI.0629-11.2011","article-title":"Spectral and temporal sensitivity of cone-mediated responses in mouse retinal ganglion cells","volume":"31","author":"Wang","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.neuron.2012.12.012","article-title":"Chromatic coding from cone-type unselective circuits in the mouse retina","volume":"77","author":"Chang","year":"2013","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e56840","DOI":"10.7554\/eLife.56840","article-title":"True S-cones are concentrated in the ventral mouse retina and wired for color detection in the upper visual field","volume":"9","author":"Kunze","year":"2020","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.tins.2011.07.001","article-title":"Intrinsically photosensitive retinal ganglion cells: Many subtypes, diverse functions","volume":"34","author":"Schmidt","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_35","first-page":"99","article-title":"Energy metabolism of the visual system","volume":"2","year":"2010","journal-title":"Eye Brain"},{"key":"ref_36","first-page":"1310","article-title":"Cre-mediated recombination efficiency and transgene expression patterns of three retinal bipolar cell-expressing Cre transgenic mouse lines","volume":"19","author":"Lu","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.cell.2008.06.016","article-title":"A mitochondrial protein compendium elucidates complex I disease biology","volume":"134","author":"Pagliarini","year":"2008","journal-title":"Cell"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1126\/science.982063","article-title":"Rod outer segment disk shedding in rat retina: Relationship to cyclic lighting","volume":"194","author":"LaVail","year":"1976","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.cub.2008.10.029","article-title":"ATP consumption by mammalian rod photoreceptors in darkness and in light","volume":"18","author":"Okawa","year":"2008","journal-title":"Curr. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1242\/jeb.017574","article-title":"Energy limitation as a selective pressure on the evolution of sensory systems","volume":"211","author":"Niven","year":"2008","journal-title":"J. Exp. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.cell.2015.03.023","article-title":"Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis","volume":"161","author":"Fridlich","year":"2015","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eaba7232","DOI":"10.1126\/sciadv.aba7232","article-title":"Molecular and functional architecture of the mouse photoreceptor network","volume":"6","author":"Jin","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.brainres.2016.12.019","article-title":"Bipolar cell reduction precedes retinal ganglion neuron loss in a complex 1 knockout mouse model","volume":"1657","author":"Song","year":"2017","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.celrep.2015.09.075","article-title":"Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons","volume":"13","author":"Kim","year":"2015","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"69","DOI":"10.5483\/BMBRep.2016.49.2.006","article-title":"Donating Otx2 to support neighboring neuron survival","volume":"49","author":"Kim","year":"2016","journal-title":"BMB Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s00439-001-0660-8","article-title":"The role of mtDNA background in disease expression: A new primary LHON mutation associated with Western Eurasian haplogroup J","volume":"110","author":"Brown","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/79936","article-title":"Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy","volume":"26","author":"Delettre","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/79944","article-title":"OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28","volume":"26","author":"Alexander","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1017\/S0952523800005666","article-title":"N-methyl-D-aspartate-induced neurotoxicity in the adult rat retina","volume":"8","author":"Siliprandi","year":"1992","journal-title":"Vis. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1056\/NEJM199403033300907","article-title":"Excitatory amino acids as a final common pathway for neurologic disorders","volume":"330","author":"Lipton","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_52","first-page":"414","article-title":"Excitatory amino acid receptors, excitotoxicity, and the human nervous system","volume":"6","author":"Shaw","year":"1993","journal-title":"Curr. Opin. Neurol. Neurosurg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/brain\/awq007","article-title":"Multi-system neurological disease is common in patients with OPA1 mutations","volume":"133","author":"Griffiths","year":"2010","journal-title":"Brain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1093\/nar\/12.4.2127","article-title":"Detection and identification of mutagens and carcinogens as their adducts with guanosine derivatives","volume":"12","author":"Kasai","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.genet.36.042602.094806","article-title":"Origins of spontaneous mutations: Specificity and directionality of base-substitution, frameshift, and sequence-substitution mutageneses","volume":"36","author":"Maki","year":"2002","journal-title":"Annu. Rev. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.dnarep.2006.03.003","article-title":"MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides","volume":"5","author":"Nakabeppu","year":"2006","journal-title":"DNA Repair"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e25946","DOI":"10.7554\/eLife.25946","article-title":"Glycolytic reliance promotes anabolism in photoreceptors","volume":"6","author":"Chinchore","year":"2017","journal-title":"eLife"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1085\/jgp.77.6.667","article-title":"Glycolytic and oxidative metabolism in relation to retinal function","volume":"77","author":"Winkler","year":"1981","journal-title":"J. Gen. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"107606","DOI":"10.1016\/j.celrep.2020.107606","article-title":"Succinate Can Shuttle Reducing Power from the Hypoxic Retina to the O2-Rich Pigment Epithelium","volume":"31","author":"Bisbach","year":"2020","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16588","DOI":"10.1073\/pnas.0405496101","article-title":"Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin","volume":"101","author":"Nishimura","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"34042","DOI":"10.1038\/srep34042","article-title":"Ska3 Ensures Timely Mitotic Progression by Interacting Directly with Microtubules and Ska1 Microtubule Binding Domain","volume":"6","author":"Abad","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12935-018-0670-4","article-title":"SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K\/Akt signaling pathway","volume":"18","author":"Hu","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0896-6273(04)00017-0","article-title":"Cell cycle activation linked to neuronal cell death initiated by DNA damage","volume":"41","author":"Kruman","year":"2004","journal-title":"Neuron"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/14\/2203\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:50:48Z","timestamp":1760140248000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/14\/2203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":63,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cells11142203"],"URL":"https:\/\/doi.org\/10.3390\/cells11142203","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]}}}