ReviewMitochondrial autophagy in neural function, neurodegenerative disease, neuron cell death, and aging

Macroautophagy is a cellular process by which cytosolic components and organelles are degraded in double-membrane bound structures upon fusion with lysosomes. A pathway for selective degradation of mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to neurons, because of the constant need for high levels of energy production in this cell type. Although much remains to be learned about mitophagy, it appears that the regulation of mitophagy shares key steps with the macroautophagy pathway, while exhibiting distinct regulatory steps specific for mitochondrial autophagic turnover. Mitophagy is emerging as an important pathway in neurodegenerative disease, and has been linked to the pathogenesis of Parkinson's disease through the study of recessively inherited forms of this disorder, involving PINK1 and Parkin. Recent work indicates that PINK1 and Parkin together maintain mitochondrial quality control by regulating mitophagy. In the Purkinje cell degeneration (pcd) mouse, altered mitophagy may contribute to the dramatic neuron cell death observed in the cerebellum, suggesting that over-active mitophagy or insufficient mitophagy can both be deleterious. Finally, mitophagy has been linked to aging, as impaired macroautophagy over time promotes mitochondrial dysfunction associated with the aging process. Understanding the role of mitophagy in neural function, neurodegenerative disease, and aging represents an essential goal for future research in the autophagy field. This article is part of a Special Issue entitled “Autophagy and protein degradation in neurological diseases.”

Research Highlights► Mitophagy shares key features with macroautophagy, but exhibits unique steps, too. ► Studies of Parkinson's disease revealed genes whose function is tied to mitophagy. ► These genes, Parkin and PINK1, encode proteins that may regulate mitophagy. ► Mitochondrial fission and fusion appear to intersect with mitophagy regulation. ► Altered mitophagy may contribute to neurodegenerative diseases and aging.