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Chaperone-mediated autophagy: machinery, regulation and biological consequences

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Abstract

Degradation of dysfunctional intracellular components in the lysosome system can occur through three different pathways, i.e., macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). In this review, we focus on CMA, a type of autophagy distinct from the other two autophagic pathways owing to its selectivity, saturability and competitivity by which a subset of long-lived cytosolic soluble proteins are directly delivered into the lysosomal lumen via specific receptors. CMA participates in quality control to maintain normal cell functions by clearing “old” proteins and provides energy to cells under nutritional stress. Deregulation of CMA has recently been shown to underlie some diseases, especially neurodegenerative disorders for which the decline with age in the activity of CMA may become a major aggravating factor. Therefore, targeting aberrant alteration in CMA under pathological conditions could serve as a potential therapeutic strategy for treating related diseases.

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Acknowledgments

We thank Brian Ciliax and Gary Miller for their critical comments. This work was supported by NIH grants (AG023695, NS048254, ES015317 and ES016731-0002) and a Michael J. Fox Foundation grant to Z. Mao.

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  1. Departments of Pharmacology and Neurology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Wenming Li, Qian Yang & Zixu Mao

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  1. Wenming Li
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Correspondence to Zixu Mao.

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Li, W., Yang, Q. & Mao, Z. Chaperone-mediated autophagy: machinery, regulation and biological consequences. Cell. Mol. Life Sci. 68, 749–763 (2011). https://doi.org/10.1007/s00018-010-0565-6

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