Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
CNC.IBILI, University of Coimbra, Coimbra, Portugal.
Essays Biochem. 2017 Dec 12;61(6):663-674. doi: 10.1042/EBC20170057.
Chaperone-mediated autophagy (CMA) is a selective form of autophagy in which cytosolic proteins bearing a pentapeptide motif biochemically related to the KFERQ sequence, are recognized by the heat shock protein family A member 8 (HSPA8) chaperone, delivered to the lysomal membrane, and directly translocated across the lysosomal membrane by a protein complex containing lysosomal associated membrane protein 2a (Lamp2a). Since its discovery over two decades ago, the importance of this pathway in cell proteostasis has been made increasingly apparent. Deregulation of this pathway has been implicated in a variety of diseases and conditions, including lysosomal storage diseases, cancer, neurodegeneration and even aging. Here, we describe the main molecular features of the pathway, its regulation, cross-talk with other degradation pathways and importance in disease.
伴侣蛋白介导的自噬（CMA）是一种选择性的自噬形式，其中含有与 KFERQ 序列在生化上相关的五肽基序的细胞质蛋白被热休克蛋白家族 A 成员 8（HSPA8）伴侣蛋白识别，递送至溶酶体膜，并直接由包含溶酶体相关膜蛋白 2a（Lamp2a）的蛋白复合物跨溶酶体膜转运。自二十多年前发现以来，该途径在细胞蛋白质稳态中的重要性变得越来越明显。该途径的失调与多种疾病和病症有关，包括溶酶体贮积病、癌症、神经退行性变甚至衰老。在这里，我们描述了该途径的主要分子特征、其调节、与其他降解途径的相互作用以及在疾病中的重要性。
