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

NEUROBIOLOGY OF DISEASE

卷:43

Review

Batlevi, Yakup¹  La Spada, Albert R.^1,2,3,4 

[1] Univ Calif San Diego, Div Genet, Dept Pediat, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Cell & Mol Biol, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[4] Rady Childrens Hosp, San Diego, CA 92123 USA

关键词: Autophagy;    Macroautophagy;    Mitophagy;    Lysosome;    Parkin;    PINK1;    Parkinson's disease;    Alzheimer's disease;    Huntington's disease;    Mitochondrial dynamics;    Fission;    Fusion;    Aging;   

DOI  :  10.1016/j.nbd.2010.09.009

来源: Elsevier

【 摘 要 】

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. (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

Free