Mitochondrial defect in muscle precedes neuromuscular junction degeneration and motor neuron death in CHCHD10
Amyotrophic Lateral Sclerosis
/ genetics
Animals
Cell Death
/ genetics
DNA-Binding Proteins
/ metabolism
Frontotemporal Dementia
/ genetics
Mice, Transgenic
Mitochondria
/ pathology
Mitochondrial Proteins
/ metabolism
Motor Neurons
/ metabolism
Nerve Degeneration
/ genetics
Neuromuscular Junction
/ metabolism
Phenotype
ALS
CHCHD10
Mitochondrial disorder
Mouse model
iPSC
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
14
12
2018
accepted:
08
03
2019
revised:
21
02
2019
pubmed:
16
3
2019
medline:
22
7
2020
entrez:
16
3
2019
Statut:
ppublish
Résumé
Recently, we provided genetic basis showing that mitochondrial dysfunction can trigger motor neuron degeneration, through identification of CHCHD10 encoding a mitochondrial protein. We reported patients, carrying the p.Ser59Leu heterozygous mutation in CHCHD10, from a large family with a mitochondrial myopathy associated with motor neuron disease (MND). Rapidly, our group and others reported CHCHD10 mutations in amyotrophic lateral sclerosis (ALS), frontotemporal dementia-ALS and other neurodegenerative diseases. Here, we generated knock-in (KI) mice, carrying the p.Ser59Leu mutation, that mimic the mitochondrial myopathy with mtDNA instability displayed by the patients from our original family. Before 14 months of age, all KI mice developed a fatal mitochondrial cardiomyopathy associated with enhanced mitophagy. CHCHD10
Identifiants
pubmed: 30874923
doi: 10.1007/s00401-019-01988-z
pii: 10.1007/s00401-019-01988-z
doi:
Substances chimiques
DNA-Binding Proteins
0
Mitochondrial Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
123-145Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-16-CE16-0024-01
Pays : International
Organisme : Agence Nationale de la Recherche
ID : ANR-11-INBS-0011-NeurATRIS
Pays : International
Organisme : AFM-Téléthon
ID : #20947
Pays : International