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Dysfunction of chaperone-mediated autophagy in human diseases

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Abstract

Chaperone-mediated autophagy (CMA), one of the degradation pathways of proteins, is highly selective to substrates that have KFERQ-like motif. In this process, the substrate proteins are first recognized by the chaperone protein, heat shock cognate protein 70 (Hsc70), then delivered to lysosomal membrane surface where the single-span lysosomal receptor, lysosome-associated membrane protein type 2A (LAMP2A) can bind to the substrate proteins to form a 700 kDa protein complex that allows them to translocate into the lysosome lumen to be degraded by the hydrolytic enzymes. This degradation pathway mediated by CMA plays an important role in regulating glucose and lipid metabolism, transcription, DNA reparation, cell cycle, cellular response to stress and consequently, regulating many aging-associated human diseases, such as neurodegeneration, cancer and metabolic disorders. In this review, we provide an overview of current research on the functional roles of CMA primarily from a perspective of understanding and treating human diseases and also discuss its potential applications for diseases.

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Funding

This work was supported by Qingdao Applied Basic Research Program Youth Project: 19-6-2-59-cg and China Postdoctoral Science Foundation Funded Project: 2015M57074, 2016T90612.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, China

    Zhaozhong Liao, Wenjing Liu, Qian Xu, Lin Hou & Ning Li

  2. College of Electronic Information, Micro-Nano Technology College, Qingdao University, Qingdao, China

    Bin Wang

  3. Department of Laboratory, The Affiliated Women and Children’s Hospital of Qingdao University, Qingdao University, Qingdao, China

    Jinlian Song

  4. Biotherapy Center, Clinical Laboratory, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, China

    Qingming Guo

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Liao, Z., Wang, B., Liu, W. et al. Dysfunction of chaperone-mediated autophagy in human diseases. Mol Cell Biochem 476, 1439–1454 (2021). https://doi.org/10.1007/s11010-020-04006-z

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