Altered mitochondrial dynamics in a novel cellular model of Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a disease that is caused by mutations in mitochondrial DNA resulting in vision loss due to retinal ganglion cell (RGC) degeneration. The exact pathophysiological mechanism causing RGC degeneration is poorly understood. This is partly due to a lack of a suitable model system. We created a novel cellular model for investigating mitochondrial dynamics in LHON by treating human dermal fibroblasts carrying the most prevalent G11778A LHON mutation with staurosporine (STSP). This treatment induced cytoplasmic protrusions resembling neurites. Mitochondrial movement was impaired in LHON fibroblasts compared to wild-type fibroblasts under conditions that induce oxidative phosphorylation (OXPHOS) but could not be attributed to reduced cytosolic ATP levels. Furthermore, LHON fibroblasts displayed altered mitochondrial network remodeling under conditions that induced OXPHOS. Our results demonstrate altered mitochondrial dynamics in LHON fibroblasts which may have implications in the pathogenesis of LHON in RGCs.