har-1/CHCHD10 mutations induce neurodegeneration and mitochondrial fragmentation in Caenorhabditis elegans

har-1/CHCHD10 突变导致秀丽隐杆线虫神经退行性变和线粒体断裂

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Abstract

CHCHD10 encodes a mitochondrial protein that plays a role in cristae morphology and oxidative phosphorylation, with mutations associated with neurodegenerative diseases, including the spectrum of amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD). The Caenorhabditis elegans ortholog of CHCHD10 is har-1 , which can be used to model CHCHD10-related neurodegenerative diseases. We focused on two har-1 mutant strains: one featuring a 260 bp deletion ( gk3124 ) and the other with a G73E point mutation ( ad2155 ). Both har-1 mutants displayed progressive paralysis, degeneration of GABAergic motor neurons, and mitochondrial fragmentation. These strains may be valuable tools for investigating pathogenic mechanisms and therapeutic strategies for neurodegenerative diseases.

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