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Lookup NU author(s): Dr Florence Burte, Dr Patrick Yu Wai Man
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
CHCHD10-related diseases include mitochondrial DNA instability disorder, frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) clinical spectrum, late-onset spinal motor neuropathy (SMAJ), and Charcot-Marie-Tooth disease type 2 (CMT2). Here, we show that CHCHD10 resides with mitofilin, CHCHD3 and CHCHD6 within the "mitochondrial contact site and cristae organizing system" (MICOS) complex. CHCHD10 mutations lead to MICOS complex disassembly and loss of mitochondrial cristae with a decrease in nucleoid number and nucleoid disorganization. Repair of the mitochondrial genome after oxidative stress is impaired in CHCHD10 mutant fibroblasts and this likely explains the accumulation of deleted mtDNA molecules in patient muscle. CHCHD10 mutant fibroblasts are not defective in the delivery of mitochondria to lysosomes suggesting that impaired mitophagy does not contribute to mtDNA instability. Interestingly, the expression of CHCHD10 mutant alleles inhibits apoptosis by preventing cytochrome c release.
Author(s): Genin EC, Plutino M, Bannwarth S, Villa E, Cisneros-Barroso E, Roy M, Ortega-Vila B, Fragaki K, Lespinasse F, Pinero-Martos E, Auge G, Moore D, Burte F, Lacas-Gervais S, Kageyama Y, Itoh K, Yu-Wai-Man P, Sesaki H, Ricci JE, Vives-Bauza C, Paquis-Flucklinger V
Publication type: Article
Publication status: Published
Journal: EMBO Molecular Medicine
Year: 2016
Volume: 8
Issue: 1
Pages: 58-72
Print publication date: 01/01/2016
Online publication date: 14/12/2015
Acceptance date: 16/11/2015
Date deposited: 09/03/2016
ISSN (print): 1757-4676
ISSN (electronic): 1757-4684
Publisher: Wiley-Blackwell Publishing Ltd.
URL: http://dx.doi.org/10.15252/emmm.201505496
DOI: 10.15252/emmm.201505496
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