{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:53:05Z","timestamp":1790837585519,"version":"4.1.0"},"reference-count":86,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":223,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100006955","name":"Office of Extramural Research, National Institutes of Health","doi-asserted-by":"publisher","award":["R03 NS099953 R21 NS101145 R01 NS081366"],"award-info":[{"award-number":["R03 NS099953 R21 NS101145 R01 NS081366"]}],"id":[{"id":"10.13039\/100006955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R03 NS099953 R21 NS101145 R01 NS081366"],"award-info":[{"award-number":["R03 NS099953 R21 NS101145 R01 NS081366"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002108","name":"Friedreich's Ataxia Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 AG050886"],"award-info":[{"award-number":["P30 AG050886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005946","name":"Jackson Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin (FXN). Most FRDA patients are homozygous for large expansions of GAA repeat sequences in intron\u00a01 of FXN, whereas a fraction of patients are compound heterozygotes, with a missense or nonsense mutation in one FXN allele and expanded GAAs in the other. A prevalent missense mutation among FRDA patients changes a glycine at position\u00a0130 to valine (G130V). Herein, we report generation of the first mouse model harboring an Fxn point mutation. Changing the evolutionarily conserved glycine\u00a0127 in mouse Fxn to valine results in a failure-to-thrive phenotype in homozygous animals and a substantially reduced number of offspring. Like G130V in FRDA, the G127V mutation results in a dramatic decrease of Fxn protein without affecting transcript synthesis or splicing. FxnG127V mouse embryonic fibroblasts exhibit significantly reduced proliferation and increased cell senescence. These defects are evident in early passage cells and are exacerbated at later passages. Furthermore, increased frequency of mitochondrial DNA lesions and fragmentation are accompanied by marked amplification of mitochondrial DNA in FxnG127V cells. Bioenergetics analyses demonstrate higher sensitivity and reduced cellular respiration of FxnG127V cells upon alteration of fatty acid availability. Importantly, substitution of FxnWT with FxnG127V is compatible with life, and cellular proliferation defects can be rescued by mitigation of oxidative stress via hypoxia or induction of the NRF2 pathway. We propose FxnG127V cells as a simple and robust model for testing therapeutic approaches for FRDA.<\/jats:p>","DOI":"10.1242\/dmm.045229","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T14:24:32Z","timestamp":1593095072000},"source":"Crossref","is-referenced-by-count":19,"title":["Mitochondrial damage and senescence phenotype of cells derived from a novel frataxin G127V point mutation mouse model of Friedreich's ataxia"],"prefix":"10.1242","volume":"13","author":[{"given":"Daniel","family":"Fil","sequence":"first","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Biochemistry and Molecular Genetics , , 1825 University Boulevard , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balu K.","family":"Chacko","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 2 Department of Pathology , , 901 19th Street South, Birmingham, AL 35294 , USA"},{"name":"Center for Free Radical Biology, University of Alabama at Birmingham 3 , Birmingham, AL 35294 , USA"},{"name":"University of Alabama at Birmingham 4 Mitochondrial Medicine Laboratory , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robbie","family":"Conley","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Biochemistry and Molecular Genetics , , 1825 University Boulevard , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosen","family":"Ouyang","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 2 Department of Pathology , , 901 19th Street South, Birmingham, AL 35294 , USA"},{"name":"Center for Free Radical Biology, University of Alabama at Birmingham 3 , Birmingham, AL 35294 , USA"},{"name":"University of Alabama at Birmingham 4 Mitochondrial Medicine Laboratory , , Birmingham, AL 35294 , USA"},{"name":"5 Department of Veteran Affairs Medical Center, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 2 Department of Pathology , , 901 19th Street South, Birmingham, AL 35294 , USA"},{"name":"Center for Free Radical Biology, University of Alabama at Birmingham 3 , Birmingham, AL 35294 , USA"},{"name":"University of Alabama at Birmingham 4 Mitochondrial Medicine Laboratory , , Birmingham, AL 35294 , USA"},{"name":"5 Department of Veteran Affairs Medical Center, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M.","family":"Darley-Usmar","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 2 Department of Pathology , , 901 19th Street South, Birmingham, AL 35294 , USA"},{"name":"Center for Free Radical Biology, University of Alabama at Birmingham 3 , Birmingham, AL 35294 , USA"},{"name":"University of Alabama at Birmingham 4 Mitochondrial Medicine Laboratory , , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aamir R.","family":"Zuberi","sequence":"additional","affiliation":[{"name":"The Rare and Orphan Disease Center, JAX Center for Precision Genetics 6 , 600 Main Street, Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen M.","family":"Lutz","sequence":"additional","affiliation":[{"name":"The Rare and Orphan Disease Center, JAX Center for Precision Genetics 6 , 600 Main Street, Bar Harbor, ME 04609 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Napierala","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Biochemistry and Molecular Genetics , , 1825 University Boulevard , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5141-0822","authenticated-orcid":false,"given":"Jill S.","family":"Napierala","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 1 Department of Biochemistry and Molecular Genetics , , 1825 University Boulevard , Birmingham, AL 35294 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"2024061302433279600_DMM045229C1","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3389\/fncel.2018.00188","article-title":"Novel Nrf2-inducer prevents mitochondrial defects and oxidative stress in Friedreich's ataxia models","volume":"12","author":"Abeti","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"2024061302433279600_DMM045229C2","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1016\/j.cell.2019.03.045","article-title":"Hypoxia rescues frataxin loss by restoring iron sulfur cluster biogenesis","volume":"177","author":"Ast","year":"2019","journal-title":"Cell"},{"key":"2024061302433279600_DMM045229C3","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/acn3.322","article-title":"Deep sequencing of mitochondrial genomes reveals increased mutation load in Friedreich's ataxia","volume":"3","author":"Bhalla","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2024061302433279600_DMM045229C4","first-page":"1251","article-title":"Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion [letter]","volume":"60","author":"Bidichandani","year":"1997","journal-title":"Am. J. Hum. Genet."},{"key":"2024061302433279600_DMM045229C5","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3389\/fncel.2014.00124","article-title":"Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism","volume":"8","author":"Bolinches-Amoros","year":"2014","journal-title":"Front. Cell Neurosci."},{"key":"2024061302433279600_DMM045229C6","doi-asserted-by":"publisher","first-page":"685","DOI":"10.18388\/abp.2006_3296","article-title":"Iron-sulfur cluster proteins: electron transfer and beyond","volume":"53","author":"Brz\u00f3ska","year":"2006","journal-title":"Acta Biochim. Pol."},{"key":"2024061302433279600_DMM045229C7","doi-asserted-by":"publisher","first-page":"e6379","DOI":"10.1371\/journal.pone.0006379","article-title":"The first cellular models based on frataxin missense mutations that reproduce spontaneously the defects associated with Friedreich ataxia","volume":"4","author":"Calmels","year":"2009","journal-title":"PLoS ONE"},{"key":"2024061302433279600_DMM045229C8","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s10048-019-00594-1","article-title":"The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype","volume":"21","author":"Candayan","year":"2020","journal-title":"Neurogenetics"},{"key":"2024061302433279600_DMM045229C9","doi-asserted-by":"publisher","first-page":"5789","DOI":"10.3390\/ijms15045789","article-title":"Frataxin silencing inactivates mitochondrial Complex I in NSC34 motoneuronal cells and alters glutathione homeostasis","volume":"15","author":"Carletti","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"2024061302433279600_DMM045229C10","doi-asserted-by":"publisher","first-page":"41469","DOI":"10.1074\/jbc.M006539200","article-title":"Two-step processing of human frataxin by mitochondrial processing peptidase. Precursor and intermediate forms are cleaved at different rates","volume":"275","author":"Cavadini","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2024061302433279600_DMM045229C11","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1093\/hmg\/9.17.2523","article-title":"Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae","volume":"9","author":"Cavadini","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C12","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/labinvest.2013.53","article-title":"Methods for defining distinct bioenergetic profiles in platelets, lymphocytes, monocytes, and neutrophils, and the oxidative burst from human blood","volume":"93","author":"Chacko","year":"2013","journal-title":"Lab. Invest."},{"key":"2024061302433279600_DMM045229C13","doi-asserted-by":"publisher","first-page":"e30054","DOI":"10.7554\/eLife.30054","article-title":"Inducible and reversible phenotypes in a novel mouse model of Friedreich's Ataxia","volume":"6","author":"Chandran","year":"2017","journal-title":"eLife"},{"key":"2024061302433279600_DMM045229C14","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1002\/acn3.433","article-title":"Selected missense mutations impair frataxin processing in Friedreich ataxia","volume":"4","author":"Clark","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2024061302433279600_DMM045229C15","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/acn3.728","article-title":"Identification of a novel missense mutation in Friedreich's ataxia -FXN(W) (168R)","volume":"6","author":"Clark","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2024061302433279600_DMM045229C16","doi-asserted-by":"publisher","first-page":"3680","DOI":"10.1111\/j.1742-4658.2008.06512.x","article-title":"Dynamics, stability and iron-binding activity of frataxin clinical mutants","volume":"275","author":"Correia","year":"2008","journal-title":"FEBS J."},{"key":"2024061302433279600_DMM045229C17","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1002\/1531-8249(199902)45:2&lt;200::AID-ANA10&gt;3.0.CO;2-U","article-title":"Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes","volume":"45","author":"Cossee","year":"1999","journal-title":"Ann. Neurol."},{"key":"2024061302433279600_DMM045229C18","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1093\/hmg\/9.8.1219","article-title":"Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation","volume":"9","author":"Cossee","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C19","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1124\/jpet.118.252759","article-title":"Ferroptosis as a novel therapeutic target for Friedreich's ataxia","volume":"369","author":"Cotticelli","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2024061302433279600_DMM045229C20","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ymgme.2010.07.001","article-title":"A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia","volume":"101","author":"Deutsch","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"2024061302433279600_DMM045229C21","doi-asserted-by":"publisher","first-page":"30753","DOI":"10.1074\/jbc.C000407200","article-title":"Crystal structure of human frataxin","volume":"275","author":"Dhe-Paganon","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2024061302433279600_DMM045229C22","doi-asserted-by":"publisher","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024061302433279600_DMM045229C23","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.freeradbiomed.2011.08.005","article-title":"Assessing bioenergetic function in response to oxidative stress by metabolic profiling","volume":"51","author":"Dranka","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"2024061302433279600_DMM045229C24","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1097\/00019052-199608000-00009","article-title":"Genetics of movement disorders","volume":"9","author":"Durr","year":"1996","journal-title":"Curr. Opin. Neurol."},{"key":"2024061302433279600_DMM045229C25","first-page":"554","article-title":"The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia","volume":"59","author":"Filla","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"2024061302433279600_DMM045229C26","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/978-1-62703-739-6_31","article-title":"Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells","volume":"1105","author":"Furda","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"2024061302433279600_DMM045229C27","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.bbamcr.2015.01.018","article-title":"Emerging critical roles of Fe-S clusters in DNA replication and repair","volume":"1853","author":"Fuss","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"2024061302433279600_DMM045229C28","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1002\/ana.24595","article-title":"Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia","volume":"79","author":"Galea","year":"2016","journal-title":"Ann. Neurol."},{"key":"2024061302433279600_DMM045229C29","doi-asserted-by":"publisher","first-page":"e20666","DOI":"10.1371\/journal.pone.0020666","article-title":"Differential expression of PGC-1\u03b1 and metabolic sensors suggest age-dependent induction of mitochondrial biogenesis in Friedreich ataxia fibroblasts","volume":"6","author":"Garc\u00eda-Gim\u00e9nez","year":"2011","journal-title":"PLoS ONE"},{"key":"2024061302433279600_DMM045229C30","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1056\/NEJMoa1114287","article-title":"Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis","volume":"367","author":"Gold","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2024061302433279600_DMM045229C31","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"2024061302433279600_DMM045229C32","doi-asserted-by":"publisher","first-page":"e1000812","DOI":"10.1371\/journal.pgen.1000812","article-title":"Altered gene expression and DNA damage in peripheral blood cells from Friedreich's ataxia patients: cellular model of pathology","volume":"6","author":"Haugen","year":"2010","journal-title":"PLoS Genet."},{"key":"2024061302433279600_DMM045229C33","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1242\/dmm.010900","article-title":"Neurons and cardiomyocytes derived from induced pluripotent stem cells as a model for mitochondrial defects in Friedreich's ataxia","volume":"6","author":"Hick","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"2024061302433279600_DMM045229C34","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1515\/hsz-2012-0198","article-title":"Integration of cellular bioenergetics with mitochondrial quality control and autophagy","volume":"393","author":"Hill","year":"2012","journal-title":"Biol. Chem."},{"key":"2024061302433279600_DMM045229C35","doi-asserted-by":"publisher","first-page":"e134221","DOI":"10.1172\/jci.insight.134221","article-title":"Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia","volume":"5","author":"Igoillo-Esteve","year":"2020","journal-title":"JCI Insight"},{"key":"2024061302433279600_DMM045229C36","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1093\/hmg\/ddx141","article-title":"Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans","volume":"26","author":"Jasoliya","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C37","doi-asserted-by":"publisher","first-page":"e0217776","DOI":"10.1371\/journal.pone.0217776","article-title":"Dimethyl fumarate dosing in humans increases frataxin expression: a potential therapy for Friedreich's Ataxia","volume":"14","author":"Jasoliya","year":"2019","journal-title":"PLoS ONE"},{"key":"2024061302433279600_DMM045229C38","doi-asserted-by":"publisher","first-page":"3854","DOI":"10.3791\/3854","article-title":"Preparation of mouse embryonic fibroblast cells suitable for culturing human embryonic and induced pluripotent stem cells","author":"Jozefczuk","year":"2012","journal-title":"J. Vis. Exp."},{"key":"2024061302433279600_DMM045229C39","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1093\/hmg\/ddg349","article-title":"Reduction in frataxin causes progressive accumulation of mitochondrial damage","volume":"12","author":"Karthikeyan","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C40","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/sj.emboj.7600541","article-title":"Biogenesis of cytosolic ribosomes requires the essential iron-sulphur protein Rli1p and mitochondria","volume":"24","author":"Kispal","year":"2005","journal-title":"EMBO J."},{"key":"2024061302433279600_DMM045229C41","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ebiom.2017.03.020","article-title":"Mitochondria in cell senescence: is mitophagy the weakest link?","volume":"21","author":"Korolchuk","year":"2017","journal-title":"EBioMedicine"},{"key":"2024061302433279600_DMM045229C42","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1093\/hmg\/7.9.1485","article-title":"Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase","volume":"7","author":"Koutnikova","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C43","doi-asserted-by":"publisher","first-page":"356","DOI":"10.3389\/fncel.2019.00356","article-title":"Nrf2 induction re-establishes a proper neuronal differentiation program in Friedreich's ataxia neural stem cells","volume":"13","author":"La Rosa","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"2024061302433279600_DMM045229C44","doi-asserted-by":"publisher","first-page":"916","DOI":"10.3390\/ijms21030916","article-title":"The NRF2 signaling network defines clinical biomarkers and therapeutic opportunity in Friedreich's ataxia","volume":"21","author":"La Rosa","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2024061302433279600_DMM045229C45","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.bbrc.2012.01.022","article-title":"Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells","volume":"418","author":"Lefevre","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2024061302433279600_DMM045229C46","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1093\/nar\/gkt1349","article-title":"LORD-Q: a long-run real-time PCR-based DNA-damage quantification method for nuclear and mitochondrial genome analysis","volume":"42","author":"Lehle","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2024061302433279600_DMM045229C47","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1399-0004.1990.tb03566.x","article-title":"Friedreich's ataxia: a descriptive epidemiological study in an Italian population","volume":"38","author":"Leone","year":"1990","journal-title":"Clin. Genet."},{"key":"2024061302433279600_DMM045229C48","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1242\/dmm.030049","article-title":"Early VGLUT1-specific parallel fiber synaptic deficits and dysregulated cerebellar circuit in the KIKO mouse model of Friedreich ataxia","volume":"10","author":"Lin","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"2024061302433279600_DMM045229C49","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1242\/dmm.030502","article-title":"Early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in the KIKO mouse model of Friedreich ataxia","volume":"10","author":"Lin","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"2024061302433279600_DMM045229C50","doi-asserted-by":"publisher","first-page":"e0189990","DOI":"10.1371\/journal.pone.0189990","article-title":"Somatic instability of the expanded GAA repeats in Friedreich's ataxia","volume":"12","author":"Long","year":"2017","journal-title":"PLoS ONE"},{"key":"2024061302433279600_DMM045229C51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2014.12.017","article-title":"Frataxin knockdown in human astrocytes triggers cell death and the release of factors that cause neuronal toxicity","volume":"76","author":"Lor\u00eda","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"2024061302433279600_DMM045229C52","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/acn3.660","article-title":"Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia","volume":"6","author":"Lynch","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"2024061302433279600_DMM045229C53","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/s004150050601","article-title":"Typical Friedreich's ataxia without GAA expansions and GAA expansion without typical Friedreich's ataxia","volume":"247","author":"McCabe","year":"2000","journal-title":"J. Neurol."},{"key":"2024061302433279600_DMM045229C54","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0300-9084(91)90078-F","article-title":"New insights into the mitochondrial carnitine palmitoyltransferase enzyme system","volume":"73","author":"McGarry","year":"1991","journal-title":"Biochimie"},{"key":"2024061302433279600_DMM045229C55","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1093\/hmg\/ddt576","article-title":"Apoptotic cell death and altered calcium homeostasis caused by frataxin depletion in dorsal root ganglia neurons can be prevented by BH4 domain of Bcl-xL protein","volume":"23","author":"Mincheva-Tasheva","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C56","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/S0014-5793(02)02251-2","article-title":"Frataxin knockin mouse","volume":"512","author":"Miranda","year":"2002","journal-title":"FEBS Lett."},{"key":"2024061302433279600_DMM045229C57","doi-asserted-by":"publisher","first-page":"264","DOI":"10.3389\/fnmol.2017.00264","article-title":"Reversible axonal dystrophy by calcium modulation in frataxin-deficient sensory neurons of YG8R mice","volume":"10","author":"Moll\u00e1","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"2024061302433279600_DMM045229C58","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1002\/mds.23789","article-title":"Correlation of frataxin content in blood and skeletal muscle endorses frataxin as a biomarker in Friedreich ataxia","volume":"26","author":"Nachbauer","year":"2011","journal-title":"Mov. Disord."},{"key":"2024061302433279600_DMM045229C59","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1093\/hmg\/ddr187","article-title":"Silencing of frataxin gene expression triggers p53-dependent apoptosis in human neuron-like cells","volume":"20","author":"Palomo","year":"2011","journal-title":"Hum. Mol. Genet."},{"issue":"Suppl. 1","key":"2024061302433279600_DMM045229C60","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/jnc.12219","article-title":"Animal and cellular models of Friedreich ataxia","volume":"126","author":"Perdomini","year":"2013","journal-title":"J. Neurochem."},{"key":"2024061302433279600_DMM045229C61","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/nm.3510","article-title":"Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia","volume":"20","author":"Perdomini","year":"2014","journal-title":"Nat. Med."},{"key":"2024061302433279600_DMM045229C62","doi-asserted-by":"publisher","first-page":"5211","DOI":"10.3390\/ijms20205211","article-title":"Targeting NRF2 for the treatment of Friedreich's ataxia: a comparison among drugs","volume":"20","author":"Petrillo","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2024061302433279600_DMM045229C63","doi-asserted-by":"publisher","first-page":"2929","DOI":"10.1093\/nar\/19.11.2929","article-title":"Measurement of the sequence specificity of covalent DNA modification by antineoplastic agents using Taq DNA polymerase","volume":"19","author":"Ponti","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"2024061302433279600_DMM045229C64","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s100480100118","article-title":"Rescue of the Friedreich's ataxia knockout mouse by human YAC transgenesis","volume":"3","author":"Pook","year":"2001","journal-title":"Neurogenetics"},{"key":"2024061302433279600_DMM045229C65","doi-asserted-by":"publisher","first-page":"e0122942","DOI":"10.1371\/journal.pone.0122942","article-title":"RTA 408, a novel synthetic triterpenoid with broad anticancer and anti-inflammatory activity","volume":"10","author":"Probst","year":"2015","journal-title":"PLoS ONE"},{"key":"2024061302433279600_DMM045229C66","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1093\/hmg\/9.6.887","article-title":"Recent advances in the molecular pathogenesis of Friedreich ataxia","volume":"9","author":"Puccio","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C67","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/84818","article-title":"Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits","volume":"27","author":"Puccio","year":"2001","journal-title":"Nat. Genet."},{"key":"2024061302433279600_DMM045229C68","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/cpmo.21","article-title":"Analysis of mtDNA\/nDNA Ratio in Mice","volume":"7","author":"Quiros","year":"2017","journal-title":"Curr. Protoc. Mouse Biol."},{"key":"2024061302433279600_DMM045229C69","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1016\/j.bbadis.2015.08.026","article-title":"Defining the effects of storage on platelet bioenergetics: The role of increased proton leak","volume":"1852","author":"Ravi","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"2024061302433279600_DMM045229C70","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.redox.2018.04.005","article-title":"Methods for assessing mitochondrial quality control mechanisms and cellular consequences in cell culture","volume":"17","author":"Redmann","year":"2018","journal-title":"Redox. Biol."},{"key":"2024061302433279600_DMM045229C71","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1007\/s00415-012-6770-5","article-title":"Clinical use of frataxin measurement in a patient with a novel deletion in the FXN gene","volume":"260","author":"Sacc\u00e0","year":"2013","journal-title":"J. Neurol."},{"key":"2024061302433279600_DMM045229C72","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1002\/med.21567","article-title":"Dimethyl fumarate, a two-edged drug: Current status and future directions","volume":"39","author":"Saidu","year":"2019","journal-title":"Med. Res. Rev."},{"key":"2024061302433279600_DMM045229C73","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1089\/ars.2009.3015","article-title":"Friedreich ataxia: molecular mechanisms, redox considerations, and therapeutic opportunities","volume":"13","author":"Santos","year":"2010","journal-title":"Antioxid Redox Signal."},{"key":"2024061302433279600_DMM045229C74","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1006\/excr.2000.4875","article-title":"Is \u03b2-galactosidase staining a marker of senescence in vitro and in vivo?","volume":"257","author":"Severino","year":"2000","journal-title":"Exp. Cell Res."},{"key":"2024061302433279600_DMM045229C75","doi-asserted-by":"publisher","first-page":"103419","DOI":"10.1016\/j.mcn.2019.103419","article-title":"Mitochondrial dysfunction in neurons in Friedreich's ataxia","volume":"102","author":"Stepanova","year":"2020","journal-title":"Mol. Cell. Neurosci."},{"key":"2024061302433279600_DMM045229C76","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.freeradbiomed.2012.06.023","article-title":"Validation of the multiple sensor mechanism of the Keap1-Nrf2 system","volume":"53","author":"Takaya","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"2024061302433279600_DMM045229C77","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.freeradbiomed.2016.06.007","article-title":"Oxidative stress and altered lipid metabolism in Friedreich ataxia","volume":"100","author":"Tamarit","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"2024061302433279600_DMM045229C78","doi-asserted-by":"publisher","first-page":"dmm032706","DOI":"10.1242\/dmm.032706","article-title":"Adding a temporal dimension to the study of Friedreich's ataxia: the effect of frataxin overexpression in a human cell model","volume":"11","author":"Vannocci","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"2024061302433279600_DMM045229C79","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1093\/hmg\/ddr554","article-title":"A TAT-Frataxin fusion protein increases lifespan and cardiac function in a conditional Friedreich's ataxia mouse model","volume":"21","author":"Vyas","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C80","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.siny.2005.04.001","article-title":"Metabolic adaptation at birth","volume":"10","author":"Ward Platt","year":"2005","journal-title":"Semin. Fetal. Neonatal. Med."},{"key":"2024061302433279600_DMM045229C81","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1007\/s12012-010-9085-8","article-title":"Perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in non-human primates","volume":"10","author":"Westbrook","year":"2010","journal-title":"Cardiovasc. Toxicol."},{"key":"2024061302433279600_DMM045229C82","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1111\/j.1399-0004.1981.tb01052.x","article-title":"Intrafamilial correlation in Friedreich's ataxia","volume":"20","author":"Winter","year":"1981","journal-title":"Clin. Genet."},{"key":"2024061302433279600_DMM045229C83","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1093\/hmg\/8.3.425","article-title":"The Friedreich's ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis","volume":"8","author":"Wong","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"2024061302433279600_DMM045229C84","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.4155\/bio.15.118","article-title":"Stable isotopes and LC-MS for monitoring metabolic disturbances in Friedreich's ataxia platelets","volume":"7","author":"Worth","year":"2015","journal-title":"Bioanalysis"},{"key":"2024061302433279600_DMM045229C85","doi-asserted-by":"publisher","first-page":"e2003782","DOI":"10.1371\/journal.pbio.2003782","article-title":"Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of \u03b2-oxidation","volume":"16","author":"Yao","year":"2018","journal-title":"PLoS Biol."},{"key":"2024061302433279600_DMM045229C86","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.tips.2019.02.001","article-title":"Therapeutic Prospects for Friedreich's Ataxia","volume":"40","author":"Zhang","year":"2019","journal-title":"Trends Pharmacol. Sci."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.045229","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.045229\/3485078\/dmm045229.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.045229\/2065873\/dmm_045229v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.045229\/3485078\/dmm045229.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:43:56Z","timestamp":1718246636000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/13\/7\/dmm045229\/225166\/Mitochondrial-damage-and-senescence-phenotype-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,1]]},"references-count":86,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.045229","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7,1]]},"article-number":"dmm045229"}}