Department of Developmental and Molecular Biology, Institute for Aging Research, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, USA.
Neurobiol Dis. 2011 Jul;43(1):29-37. doi: 10.1016/j.nbd.2010.07.006. Epub 2010 Jul 17.
Chaperone-mediated autophagy (CMA) contributes to selective degradation of individual soluble proteins in lysosomes. Unique to this type of autophagy is the fact that proteins reach the lysosomal lumen for degradation by directly crossing the lysosomal membrane, in contrast with the vesicle-mediated delivery characteristic of the other types of autophagy. These two characteristics--selective targeting and direct translocation of substrates--determine the contribution of CMA to different physiological functions and the type of pathological conditions associated with CMA dysfunction. In this review, we briefly revise recent findings on the molecular mechanisms behind CMA function, and describe the physiological relevance of the selective lysosomal degradation through this pathway. We also comment on the cellular consequences of CMA malfunction and on the connections already established between CMA dysfunction and different human disorders, with special emphasis on neurodegenerative diseases. This article is part of a Special Issue entitled "Autophagy and protein degradation in neurological diseases."
伴侣蛋白介导的自噬（CMA）有助于溶酶体中个别可溶性蛋白的选择性降解。这种自噬的独特之处在于，与其他类型的自噬所特有的囊泡介导的递呈不同，蛋白质通过直接穿过溶酶体膜到达溶酶体腔进行降解。这两个特性——底物的选择性靶向和直接易位——决定了 CMA 对不同生理功能的贡献以及与 CMA 功能障碍相关的病理状况的类型。在这篇综述中，我们简要回顾了 CMA 功能背后的分子机制的最新发现，并描述了通过这条途径进行的选择性溶酶体降解的生理相关性。我们还评论了 CMA 故障的细胞后果，以及 CMA 功能障碍与不同人类疾病之间已经建立的联系，特别强调了神经退行性疾病。本文是题为“神经疾病中的自噬和蛋白质降解”的特刊的一部分。
