Mitochondrial Dynamics in Neurodegenerative Disease

Mitochondrial fusion plays an important role in regulating mitochondrial structure and function. Several large GTPases (OPA1 and mitofusins) are essential for mitochondrial fusion. Deletion of any of these genes in mice results in embryonic lethality, and fusion-deficient cells show severe defects in mitochondrial morphology, respiratory activity, and mtDNA nucleoids. Mutations in Mfn2 and OPA1 cause two human neuropathies, Charcot-Marie-Tooth type 2A and dominant optic atrophy. We have used mouse models to understand how defects in mitochondrial fusion lead to dysfunction in neurons. In addition, the coordination of mitochondrial fusion by mitofusins and OPA1 will be discussed.