{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:27:37Z","timestamp":1792618057211,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"9","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson\u2019s disease and amyotrophic lateral sclerosis\/frontotemporal dementia\/myopathy, respectively. The mechanism by which they disrupt mitochondrial cristae, however, has been uncertain. Using the first C2\/C10 double knockout (DKO) mice, we report that C10 pathogenesis and the normal function of C2\/C10 are intimately linked. Similar to patients with C10 mutations, we found that C2\/C10 DKO mice have disrupted mitochondrial cristae, because of cleavage of the mitochondrial-shaping protein long form of OPA1 (L-OPA1) by the stress-induced peptidase OMA1. OMA1 was found to be activated similarly in affected tissues of mutant C10 knock-in (KI) mice, demonstrating that L-OPA1 cleavage is a novel mechanism for cristae abnormalities because of both C10 mutation and C2\/C10 loss. Using OMA1 activation as a functional assay, we found that C2 and C10 are partially functionally redundant, and some but not all disease-causing mutations have retained activity. Finally, C2\/C10 DKO mice partially phenocopied mutant C10 KI mice with the development of cardiomyopathy and activation of the integrated mitochondrial integrated stress response in affected tissues, tying mutant C10 pathogenesis to C2\/C10 function.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa077","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T15:09:14Z","timestamp":1587654554000},"page":"1547-1567","source":"Crossref","is-referenced-by-count":76,"title":["Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations"],"prefix":"10.1093","volume":"29","author":[{"given":"Yi-Ting","family":"Liu","sequence":"first","affiliation":[{"name":"Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Huang","sequence":"first","affiliation":[{"name":"Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Nguyen","sequence":"first","affiliation":[{"name":"Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario K","family":"Shammas","sequence":"first","affiliation":[{"name":"Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly P","family":"Wu","sequence":"first","affiliation":[{"name":"Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Dombi","sequence":"first","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle A","family":"Springer","sequence":"first","affiliation":[{"name":"Murine Phenotyping Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Poulton","sequence":"first","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Sekine","sequence":"first","affiliation":[{"name":"Aging Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8696-9108","authenticated-orcid":false,"given":"Derek P","family":"Narendra","sequence":"first","affiliation":[{"name":"Inherited Movement Disorders Unit, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,27]]},"reference":[{"key":"2020060308500714700_ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10048-014-0421-1","article-title":"Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy","volume":"16","author":"Ajroud-Driss","year":"2015","journal-title":"Neurogenetics"},{"key":"2020060308500714700_ref2","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1093\/brain\/awu138","article-title":"A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement","volume":"137","author":"Bannwarth","year":"2014","journal-title":"Brain J. 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