Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, China.
College of Electronic Information, Micro-Nano Technology College, Qingdao University, Qingdao, China.
Mol Cell Biochem. 2021 Mar;476(3):1439-1454. doi: 10.1007/s11010-020-04006-z. Epub 2021 Jan 3.
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.
伴侣蛋白介导的自噬（CMA）是蛋白质降解途径之一，对具有 KFERQ 样基序的底物具有高度选择性。在这个过程中，底物蛋白首先被伴侣蛋白热休克同源蛋白 70（Hsc70）识别，然后递送到溶酶体膜表面，溶酶体相关膜蛋白 2A（LAMP2A）的单跨溶酶体受体可以与底物蛋白结合形成一个 700 kDa 的蛋白质复合物，允许它们转运到溶酶体腔中被水解酶降解。这种由 CMA 介导的降解途径在调节葡萄糖和脂质代谢、转录、DNA 修复、细胞周期、细胞对压力的反应以及调节许多与衰老相关的人类疾病（如神经退行性疾病、癌症和代谢紊乱）方面发挥着重要作用。在这篇综述中，我们从理解和治疗人类疾病的角度，对 CMA 的功能作用的当前研究进行了概述，并讨论了其在疾病治疗方面的潜在应用。
