OPA1 in mitochondrial quality control and its implications for RGC degeneration

Abstract Mitochondria are vulnerable to damages of their proteins, lipids, and mtDNA by various stress factors and mitochondria either recycle dysfunctional mitochondria via the mitochondrial autophagy pathway, arrange for the recycling of the complete host cell by apoptosis, or continue to function normally and supply the host with energy and metabolites. This is called mitochondrial quality control and it is crucial for all neurodegenerative diseases, including the most prominent ones, Alzheimer’s disease and Parkinson’s disease. Mitochondrial quality control is facilitated by mitochondrial network dynamics – continuous fission and fusion of mitochondria. Mitochondrial fission is accomplished by DRP1. MFN1 and MFN2 on the mitochondrial outer membrane, and OPA1 on the mitochondrial inner membrane are necessary for mitochondrial fusion. Mitochondrial network dynamics are regulated in highly sophisticated ways by post‐translational modifications and protein processing. I would like to present selected aspects of mitochondrial quality control using OPA1 as an example and discuss their implication on Dominant Optic Atrophy, a slowly progressive optic neuropathy with juvenile onset caused by mutations in the OPA1 gene.