{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T01:15:19Z","timestamp":1775610919545,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Discov."],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Autosomal dominant optic atrophy (ADOA) caused by mutations in the nuclear-encoded OPA1 gene result in the preferential loss of retinal ganglion cells (RGCs) and progressive optic nerve degeneration. The severity of ADOA can be highly variable. This study compared the pathophysiological consequences of the c.1034\u2009G\u2009&gt;\u2009A OPA1 missense mutation and the c.1305+2delGT OPA1 deletion. There was a significant correlation between the severity of visual loss and the extent of macular RGC loss as determined by optical coherence tomography imaging. In cells transfected with the c.1034\u2009G\u2009&gt;\u2009A mutant, the percentage of fragmented mitochondria was greater than 60% with cytochrome c (cyt c) overflow, and significantly elevated levels of reactive oxygen species (ROS) and apoptosis. In contrast, the c.1305+2delGT mutant caused mitochondrial fragmentation in ~ 20% of HeLa cells, resulting in less cyt c overflow and apoptosis. The extent of mitochondrial network fragmentation and apoptosis increased with decreasing WT OPA1 mRNA expression levels. The c.1034\u2009G\u2009&gt;\u2009A OPA1 missense mutation is likely to induce a dominant-negative effect compared with haploinsufficiency with the c.1305+2delGT OPA1 deletion. These contrasting pathophysiological mechanisms could influence disease severity in ADOA through their differential consequences on mitochondrial structure and function. The small drug molecule Paromomycin was able to rescue the mitochondrial fragmentation induced by the c.1034\u2009G\u2009&gt;\u2009A mutation, providing proof-of-concept for further therapeutic validation in ADOA.<\/jats:p>","DOI":"10.1038\/s41420-025-02442-8","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T06:34:20Z","timestamp":1748586860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Contrasting pathophysiological mechanisms of OPA1 mutations in autosomal dominant optic atrophy"],"prefix":"10.1038","volume":"11","author":[{"given":"Shi-Qi","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Jian","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoying","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjie","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong-Bo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruixi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tai-Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Fang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Jie","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Yu-Wai-Man","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihui","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3876-0606","authenticated-orcid":false,"given":"Ling-Ping","family":"Cen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"2442_CR1","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1016\/j.ophtha.2009.12.038","volume":"117","author":"P Yu-Wai-Man","year":"2010","unstructured":"Yu-Wai-Man P, Griffiths PG, Burke A, Sellar PW, Clarke MP, Gnanaraj L, et al. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. Ophthalmology 2010;117:1538\u201346.","journal-title":"Ophthalmology"},{"key":"2442_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05571-y","volume":"7","author":"J Zhang","year":"2017","unstructured":"Zhang J, Liu X, Liang X, Lu Y, Zhu L, Fu R, et al. A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis. Sci Rep. 2017;7:5704.","journal-title":"Sci Rep"},{"key":"2442_CR3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","volume":"30","author":"P Yu-Wai-Man","year":"2011","unstructured":"Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. Prog Retinal Eye Res. 2011;30:81\u2013114.","journal-title":"Prog Retinal Eye Res"},{"key":"2442_CR4","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1016\/0002-9394(79)90565-8","volume":"88","author":"PB Johnston","year":"1979","unstructured":"Johnston PB, Gaster RN, Smith VC, Tripathi RC. A clinicopathologic study of autosomal dominant optic atrophy. Am J Ophthalmol. 1979;88:868\u201375.","journal-title":"Am J Ophthalmol"},{"key":"2442_CR5","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1111\/j.1755-3768.1983.tb01424.x","volume":"61","author":"P Kjer","year":"1983","unstructured":"Kjer P, Jensen OA, Klinken L. Histopathology of eye, optic nerve and brain in a case of dominant optic atrophy. Acta ophthalmologica. 1983;61:300\u201312.","journal-title":"Acta ophthalmologica"},{"key":"2442_CR6","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/79936","volume":"26","author":"C Delettre","year":"2000","unstructured":"Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet. 2000;26:207\u201310.","journal-title":"Nat Genet"},{"key":"2442_CR7","doi-asserted-by":"publisher","first-page":"e110","DOI":"10.1136\/jmg.2003.016576","volume":"41","author":"P Reynier","year":"2004","unstructured":"Reynier P, Amati-Bonneau P, Verny C, Olichon A, Simard G, Guichet A, et al. OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract. J Med Genet. 2004;41:e110.","journal-title":"J Med Genet"},{"key":"2442_CR8","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1001\/archopht.117.6.805","volume":"117","author":"JB Kerrison","year":"1999","unstructured":"Kerrison JB, Arnould VJ, Ferraz Sallum JM, Vagefi MR, Barmada MM, Li Y, et al. Genetic heterogeneity of dominant optic atrophy, Kjer type: Identification of a second locus on chromosome 18q12.2-12.3. Arch Ophthalmol (Chic, Ill : 1960). 1999;117:805\u201310.","journal-title":"Arch Ophthalmol (Chic, Ill : 1960)"},{"key":"2442_CR9","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1136\/jmg.2004.025502","volume":"42","author":"F Barbet","year":"2005","unstructured":"Barbet F, Hakiki S, Orssaud C, Gerber S, Perrault I, Hanein S, et al. A third locus for dominant optic atrophy on chromosome 22q. J Med Genet. 2005;42:e1.","journal-title":"J Med Genet"},{"key":"2442_CR10","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1146\/annurev.biochem.76.071905.090048","volume":"76","author":"S Hoppins","year":"2007","unstructured":"Hoppins S, Lackner L, Nunnari J. The machines that divide and fuse mitochondria. Annu Rev Biochem. 2007;76:751\u201380.","journal-title":"Annu Rev Biochem"},{"key":"2442_CR11","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/S0955-0674(03)00070-X","volume":"15","author":"SV Scott","year":"2003","unstructured":"Scott SV, Cassidy-Stone A, Meeusen SL, Nunnari J. Staying in aerobic shape: how the structural integrity of mitochondria and mitochondrial DNA is maintained. Curr Opin cell Biol. 2003;15:482\u20138.","journal-title":"Curr Opin cell Biol"},{"key":"2442_CR12","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1023\/B:MCBI.0000009879.01256.f6","volume":"256-257","author":"DA Rube","year":"2004","unstructured":"Rube DA, van der Bliek AM. Mitochondrial morphology is dynamic and varied. Mol Cell Biochem. 2004;256-257:331\u20139.","journal-title":"Mol Cell Biochem"},{"key":"2442_CR13","doi-asserted-by":"publisher","first-page":"7743","DOI":"10.1074\/jbc.C200677200","volume":"278","author":"A Olichon","year":"2003","unstructured":"Olichon A, Baricault L, Gas N, Guillou E, Valette A, Belenguer P, et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem. 2003;278:7743\u20136.","journal-title":"J Biol Chem"},{"key":"2442_CR14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","volume":"126","author":"C Frezza","year":"2006","unstructured":"Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell. 2006;126:177\u201389.","journal-title":"Cell"},{"key":"2442_CR15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.phrs.2018.02.018","volume":"131","author":"V Del Dotto","year":"2018","unstructured":"Del Dotto V, Fogazza M, Lenaers G, Rugolo M, Carelli V, Zanna C. OPA1: How much do we know to approach therapy? Pharmacol Res. 2018;131:199\u2013210.","journal-title":"Pharmacol Res"},{"key":"2442_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-32","volume":"8","author":"MV Alavi","year":"2013","unstructured":"Alavi MV, Fuhrmann N. Dominant optic atrophy, OPA1, and mitochondrial quality control: understanding mitochondrial network dynamics. Mol neurodegeneration. 2013;8:32.","journal-title":"Mol neurodegeneration"},{"key":"2442_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-25","volume":"5","author":"N Fuhrmann","year":"2010","unstructured":"Fuhrmann N, Schimpf S, Kamenisch Y, Leo-Kottler B, Alexander C, Auburger G, et al. Solving a 50 year mystery of a missing OPA1 mutation: more insights from the first family diagnosed with autosomal dominant optic atrophy. Mol neurodegeneration. 2010;5:25.","journal-title":"Mol neurodegeneration"},{"key":"2442_CR18","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.ajo.2004.06.011","volume":"138","author":"M Payne","year":"2004","unstructured":"Payne M, Yang Z, Katz BJ, Warner JE, Weight CJ, Zhao Y, et al. Dominant optic atrophy, sensorineural hearing loss, ptosis, and ophthalmoplegia: a syndrome caused by a missense mutation in OPA1. Am J Ophthalmol. 2004;138:749\u201355.","journal-title":"Am J Ophthalmol"},{"key":"2442_CR19","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1002\/jcp.20950","volume":"211","author":"A Olichon","year":"2007","unstructured":"Olichon A, Landes T, Arnaun\u00e9-Pelloquin L, Emorine LJ, Mils V, Guichet A, et al. Effects of OPA1 mutations on mitochondrial morphology and apoptosis: relevance to ADOA pathogenesis. J Cell Physiol. 2007;211:423\u201330.","journal-title":"J Cell Physiol"},{"key":"2442_CR20","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1007\/s12035-016-9771-z","volume":"54","author":"AM Zhang","year":"2017","unstructured":"Zhang AM, Bi R, Hu QX, Fan Y, Zhang Q, Yao YG. The OPA1 gene mutations are frequent in Han Chinese patients with suspected optic neuropathy. Mol Neurobiol. 2017;54:1622\u201330.","journal-title":"Mol Neurobiol"},{"key":"2442_CR21","doi-asserted-by":"publisher","first-page":"15927","DOI":"10.1073\/pnas.0407043101","volume":"101","author":"S Cipolat","year":"2004","unstructured":"Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci USA. 2004;101:15927\u201332.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2442_CR22","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/35065645","volume":"410","author":"B Marks","year":"2001","unstructured":"Marks B, Stowell MH, Vallis Y, Mills IG, Gibson A, Hopkins CR, et al. GTPase activity of dynamin and resulting conformation change are essential for endocytosis. Nature. 2001;410:231\u20135.","journal-title":"Nature"},{"key":"2442_CR23","doi-asserted-by":"publisher","first-page":"18792","DOI":"10.1074\/jbc.M400920200","volume":"279","author":"L Griparic","year":"2004","unstructured":"Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM. Loss of the intermembrane space protein Mgm1\/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J Biol Chem. 2004;279:18792\u20138.","journal-title":"J Biol Chem"},{"key":"2442_CR24","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.003012","volume":"1","author":"L Chen","year":"2012","unstructured":"Chen L, Liu T, Tran A, Lu X, Tomilov AA, Davies V, et al. OPA1 mutation and late-onset cardiomyopathy: mitochondrial dysfunction and mtDNA instability. J Am Heart Assoc. 2012;1:e003012.","journal-title":"J Am Heart Assoc"},{"key":"2442_CR25","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.1371\/journal.pgen.0040006","volume":"4","author":"W Yarosh","year":"2008","unstructured":"Yarosh W, Monserrate J, Tong JJ, Tse S, Le PK, Nguyen K, et al. The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet. 2008;4:e6.","journal-title":"PLoS Genet"},{"key":"2442_CR26","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cmet.2014.03.011","volume":"19","author":"P Mishra","year":"2014","unstructured":"Mishra P, Carelli V, Manfredi G, Chan DC. Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab. 2014;19:630\u201341.","journal-title":"Cell Metab"},{"key":"2442_CR27","doi-asserted-by":"publisher","first-page":"7115","DOI":"10.1074\/jbc.M116.762567","volume":"292","author":"H Lee","year":"2017","unstructured":"Lee H, Smith SB, Yoon Y. The short variant of the mitochondrial dynamin OPA1 maintains mitochondrial energetics and cristae structure. J Biol Chem. 2017;292:7115\u201330.","journal-title":"J Biol Chem"},{"key":"2442_CR28","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1016\/j.celrep.2017.05.073","volume":"19","author":"V Del Dotto","year":"2017","unstructured":"Del Dotto V, Mishra P, Vidoni S, Fogazza M, Maresca A, Caporali L, et al. OPA1 Isoforms in the Hierarchical Organization of Mitochondrial Functions. Cell Rep. 2017;19:2557\u201371.","journal-title":"Cell Rep."},{"key":"2442_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.920390","volume":"13","author":"R Kingdom","year":"2022","unstructured":"Kingdom R, Wright CF. Incomplete penetrance and variable expressivity: from clinical studies to population cohorts. Front Genet. 2022;13:920390.","journal-title":"Front Genet"},{"key":"2442_CR30","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1159\/000508050","volume":"160","author":"EN Tolmacheva","year":"2020","unstructured":"Tolmacheva EN, Kashevarova AA, Nazarenko LP, Minaycheva LI, Skryabin NA, Lopatkina ME, et al. Delineation of clinical manifestations of the inherited Xq24 microdeletion segregating with sXCI in mothers: two novel cases with distinct phenotypes ranging from UBE2A deficiency syndrome to recurrent pregnancy loss. Cytogenetic Genome Res. 2020;160:245\u201354.","journal-title":"Cytogenetic Genome Res"},{"key":"2442_CR31","doi-asserted-by":"publisher","first-page":"e1003073","DOI":"10.1371\/journal.pcbi.1003073","volume":"9","author":"WH Chen","year":"2013","unstructured":"Chen WH, Zhao XM, van Noort V, Bork P. Human monogenic disease genes have frequently functionally redundant paralogs. PLoS Comput. Biol. 2013;9:e1003073.","journal-title":"PLoS Comput. Biol"},{"key":"2442_CR32","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202010138","volume":"17","author":"L Parts","year":"2021","unstructured":"Parts L, Batt\u00e9 A, Lopes M, Yuen MW, Laver M, San Luis BJ, et al. Natural variants suppress mutations in hundreds of essential genes. Mol Syst Biol. 2021;17:e10138.","journal-title":"Mol Syst Biol"},{"key":"2442_CR33","doi-asserted-by":"publisher","first-page":"e0230566","DOI":"10.1371\/journal.pone.0230566","volume":"15","author":"E Buglo","year":"2020","unstructured":"Buglo E, Sarmiento E, Martuscelli NB, Sant DW, Danzi MC, Abrams AJ, et al. Genetic compensation in a stable slc25a46 mutant zebrafish: a case for using F0 CRISPR mutagenesis to study phenotypes caused by inherited disease. PLoS ONE. 2020;15:e0230566.","journal-title":"PLoS ONE"},{"key":"2442_CR34","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1097\/WNO.0000000000001830","volume":"43","author":"DCS Wong","year":"2023","unstructured":"Wong DCS, Harvey JP, Jurkute N, Thomasy SM, Moosajee M, Yu-Wai-Man P, et al. OPA1 dominant optic atrophy: pathogenesis and therapeutic targets. J Neuroophthalmol. 2023;43:464\u201374.","journal-title":"J Neuroophthalmol"},{"key":"2442_CR35","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.8.e47","volume":"39","author":"NJ Marchbank","year":"2002","unstructured":"Marchbank NJ, Craig JE, Leek JP, Toohey M, Churchill AJ, Markham AF, et al. Deletion of the OPA1 gene in a dominant optic atrophy family: evidence that haploinsufficiency is the cause of disease. J Med Genet. 2002;39:e47.","journal-title":"J Med Genet"},{"key":"2442_CR36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2207471120","volume":"120","author":"B Cartes-Saavedra","year":"2023","unstructured":"Cartes-Saavedra B, Lagos D, Macuada J, Arancibia D, Burt\u00e9 F, Sj\u00f6berg-Herrera MK, et al. OPA1 disease-causing mutants have domain-specific effects on mitochondrial ultrastructure and fusion. Proc Natl Acad Sci USA. 2023;120:e2207471120.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2442_CR37","doi-asserted-by":"publisher","first-page":"baad083","DOI":"10.1093\/database\/baad083","volume":"2023","author":"LP Cen","year":"2023","unstructured":"Cen LP, Ng TK, Ji J, Lin JW, Yao Y, Yang R, et al. Artificial Intelligence-based database for prediction of protein structure and their alterations in ocular diseases. Database (Oxf). 2023;2023:baad083.","journal-title":"Database (Oxf)"},{"key":"2442_CR38","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/jcc.20290","volume":"26","author":"DA Case","year":"2005","unstructured":"Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R, Merz KM Jr, et al. The Amber biomolecular simulation programs. J Comput Chem. 2005;26:1668\u201388.","journal-title":"J Comput Chem"},{"key":"2442_CR39","doi-asserted-by":"publisher","first-page":"9431","DOI":"10.3390\/ijms22179431","volume":"22","author":"AO Fadaka","year":"2021","unstructured":"Fadaka AO, Sibuyi NRS, Martin DR, Klein A, Madiehe A, Meyer M. Development of effective therapeutic molecule from natural sources against coronavirus protease. Int J Mol Sci. 2021;22:9431.","journal-title":"Int J Mol Sci"},{"key":"2442_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/srep34984","volume":"6","author":"I Aier","year":"2016","unstructured":"Aier I, Varadwaj PK, Raj U. Structural insights into conformational stability of both wild-type and mutant EZH2 receptor. Sci Rep. 2016;6:34984.","journal-title":"Sci Rep."},{"key":"2442_CR41","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1002\/ana.25723","volume":"88","author":"L Caporali","year":"2020","unstructured":"Caporali L, Magri S, Legati A, Del Dotto V, Tagliavini F, Balistreri F, et al. ATPase domain AFG3L2 mutations alter OPA1 processing and cause optic neuropathy. Ann Neurol. 2020;88:18\u201332.","journal-title":"Ann Neurol"}],"container-title":["Cell Death Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02442-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02442-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02442-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T08:04:22Z","timestamp":1748592262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41420-025-02442-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2442"],"URL":"https:\/\/doi.org\/10.1038\/s41420-025-02442-8","relation":{},"ISSN":["2058-7716"],"issn-type":[{"value":"2058-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]},"assertion":[{"value":"12 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 March 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Procedures involving human participants and data were approved by the ethics committee of Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong (JSIEC) (EC 20200512(4)-P01). The study conformed to the tenets of the Helsinki Declaration. All methods were performed in accordance with the relevant guidelines and regulations. Written informed consent was obtained from all participants or their guardians prior to the collection of clinical data, venous blood samples and publishing identifiable images.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"259"}}