C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.

ABSTRACT:

Introduction

ALS is a neurodegenerative disorder characterized by progressive upper and lower motor neuron loss. A GGGGCC hexanucleotide repeat expansion (HRE) in the C9orf72 gene is the most common mutation found in populations of European descent. Mitochondrial dysfunction has been observed in C9orf72-ALS patients and models of the disease, however, reports on mitochondrial clearance via mitophagy in C9orf72-ALS are limited.

Results

iNeurons from C9orf72-ALS patients displayed reduced mitochondrial membrane potential and reduced basal mitophagy, due to reductions in autophagosome production and reduced ULK1 recruitment to mitochondria. No consistent changes to PINK1/Parkin or BNIP3 mitophagy pathways were observed.

Conclusion

Our data show that certain aspects of mi

SUBMITTER: Lee JAK 

PROVIDER: S-EPMC12933941 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature