Impaired mitochondrial morphological plasticity and failure of mitophagy associated with the G11778A mutation of LHON

• DOI: 10.1016/j.bbrc.2024.150119
• Publication Date: 2024-05-14T01:28:15Z
• Authors: Bryce A. Pasqualotto; Alexa Nelson; Samineh Deheshi; Claire A. Sheldon; A. Wayne Vogl; Gordon L. Rintoul
• Keywords: Mutation; Mitophagy; Humans; Optic Atrophy, Hereditary, Leber; Fibroblasts; Oxidative Phosphorylation; Cells, Cultured; Mitochondria

Mitochondrial dynamics were examined in human dermal fibroblasts biopsied from a confirmed Leber's Hereditary Optic Neuropathy (LHON) patient with homoplasmic G11778A mutation of the mitochondrial genome. Expression did not impart any discernable difference network morphology using widefield fluorescence microscopy. However, at ultrastructural level, cells expressing this exhibited an impairment morphological plasticity when forced to utilize oxidative phosphorylation (OXPHOS) by transition glucose-free, galactose-containing media. LHON also displayed transient increase mitophagy upon galactose These results provide new insights into consequences and pathological mechanisms underlying disease.