Mitochondrial dynamics in cell death and neurodegeneration.

Abstract

Mitochondria are highly dynamic organelles that continuously undergo two opposite processes, fission and fusion. Mitochondrial dynamics influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within the cell, cell bioenergetics, and cell injury or death. Drp1 mediates mitochondrial fission, whereas Mfn1/2 and Opa1 control mitochondrial fusion. Neurons require large amounts of energy to carry out their highly specialized functions. Thus, mitochondrial dysfunction is a prominent feature in a variety of neurodegenerative diseases. Mutations of Mfn2 and Opa1 lead to neuropathies such as Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Moreover, both Aβ peptide and mutant huntingtin protein induce mitochondrial fragmentation and neuronal cell death. In addition, mutants of Parkinson's disease-related genes also show abnormal mitochondrial morphology. This review highlights our current understanding of abnormal mitochondrial dynamics relevant to neuronal synaptic loss and cell death in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease.