Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Proc Am Thorac Soc. 2010 Feb;7(1):29-39. doi: 10.1513/pats.200909-102JS.
Continuous renewal of intracellular components is required to preserve cellular functionality. In fact, failure to timely turnover proteins and organelles leads often to cell death and disease. Different pathways contribute to the degradation of intracellular components in lysosomes or autophagy. In this review, we focus on chaperone-mediated autophagy (CMA), a selective form of autophagy that modulates the turnover of a specific pool of soluble cytosolic proteins. Selectivity in CMA is conferred by the presence of a targeting motif in the cytosolic substrates that, upon recognition by a cytosolic chaperone, determines delivery to the lysosomal surface. Substrate proteins undergo unfolding and translocation across the lysosomal membrane before reaching the lumen, where they are rapidly degraded. Better molecular characterization of the different components of this pathway in recent years, along with the development of transgenic models with modified CMA activity and the identification of CMA dysfunction in different severe human pathologies and in aging, are all behind the recent regained interest in this catabolic pathway.
为了保持细胞功能，细胞内成分需要不断更新。事实上，如果蛋白质和细胞器不能及时更新，细胞通常会死亡并导致疾病。不同的途径有助于溶酶体或自噬中细胞内成分的降解。在这篇综述中，我们重点介绍伴侣介导的自噬（CMA），这是一种选择性自噬形式，可调节特定可溶性细胞质蛋白池的周转率。CMA 的选择性是由细胞质底物中存在靶向基序赋予的，该基序在被细胞质伴侣识别后，决定递送至溶酶体表面。底物蛋白在到达腔之前经历展开和穿过溶酶体膜的易位，在腔中它们被快速降解。近年来，对该途径的不同成分的更详细的分子特征描述，以及对 CMA 活性进行修饰的转基因模型的开发，以及在不同严重人类疾病和衰老中 CMA 功能障碍的鉴定，都使得人们对这种分解代谢途径重新产生了兴趣。
