Leber's hereditary optic neuropathy-associated ND1 3733G>C mutation ameliorates the mitochondrial quality control and cellular homeostasis.

ABSTRACT: Leber's hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy because of mitochondrial DNA (mtDNA) mutations. However, the mechanism underlying LHON-linked mtDNA mutations, especially their impact on mitochondrial and cellular integrity, is not well understood. Recently, the ND1 3733G>C (p.E143Q) mutation was identified in three Chinese pedigrees with LHON. In this study, we investigated the pathogenic mechanism of m.3733G>C mutation using cybrids generated by fusing mtDNA-less ρ⁰ cells with enucleated cells from a Chinese patient carrying the m.3733G>C mutation and control subject. Molecular dynamics simulations showed that p.E143Q mutation destabilized these interactions between residues E143 and S110/Y114 or between S141 and W290 in the ND1. Its impac

SUBMITTER: Yasheng M 

PROVIDER: S-EPMC12340437 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature