Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/20246
Title
CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis
Author(s)
Genin, Emmanuelle C | Plutino, Morgane | Bannwarth, Sylvie | Villa, Elodie | Cisneros-Barroso, Eugenia | Roy, Madhuparna | Ortega-Vila, Bernardo | Fragaki, Konstantina | Lespinasse, Francoise | Pinero-Martos, Estefania | Auge, Gaelle | Moore, David | Burte, Florence | Lacas-Gervais, Sandra | Kageyama, Yusuke | Itoh, Kie | Yu-Wai-Man, Patrick | Sesaki, Hiromi | Ricci, Jean-Ehrland | Vives-Bauza, Cristofol | Paquis-Flucklinger, Veronique
Date issued
2016-01
Citation
Genin EC, Plutino M, Bannwarth S, Villa E, Cisneros-Barroso E, Roy M, et al. CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis. EMBO Mol Med. 2016 Jan;8(1):58-72.
Language
Inglés
Document type
research article
Abstract
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.
Subject
MESH
Genome, Mitochondrial | Oxidative Stress | Mitochondria | Alleles | Humans | Cell Line | HeLa Cells | Mitochondrial Proteins | Real-Time Polymerase Chain Reaction | Cytochromes c | Hydrogen Peroxide | Lysosomes | DNA, Mitochondrial | DNA Repair | Membrane Potential, Mitochondrial | Mutation | Apoptosis | Mitochondrial Diseases
DECS
Citocromos c | Genoma Mitocondrial | Reparación del ADN | Apoptosis | Enfermedades Mitocondriales | Proteínas Mitocondriales | Línea Celular | ADN Mitocondrial | Mutación | Alelos | Células HeLa | Peróxido de Hidrógeno | Lisosomas | Reacción en Cadena en Tiempo Real de la Polimerasa | Humanos | Estrés Oxidativo | Potencial de la Membrana Mitocondrial | Mitocondrias
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