Role of GTPases in the regulation of mitochondrial dynamics in Parkinson's disease

Abstract

Mitochondria are highly dynamic organelle that undergo frequent fusion and division, and the balance of these opposing processes regulates mitochondrial morphology, distribution, and function. Mitochondrial fission facilitates the replication and distribution of mitochondria during cell division, whereas the fusion process including inner and outer mitochondrial membrane fusion allows the exchange of intramitochondrial material between adjacent mitochondria. Despite several GTPase family proteins have been implicated as key modulators of mitochondrial dynamics, the mechanisms by which these proteins regulate mitochondrial homeostasis and function remain not clearly understood. Neuronal function and survival are closely related to mitochondria dynamics, and disturbed mitochondrial fission/fusion may influence neurotransmission, synaptic maintenance, neuronal survival and function. Recent studies have shown that mitochondrial dysfunction caused by aberrant mitochondrial dynamics plays an essential role in the pathogenesis of both sporadic and familial Parkinson's disease (PD). Collectively, we review the molecular mechanism of known GTPase proteins in regulating mitochondrial fission and fusion, but also highlight the causal role for mitochondrial dynamics in PD pathogenesis.