Franch Harold A
Research Service, Atlanta Veterans Affairs Medical Center, Decatur, GA; and Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
Semin Nephrol. 2014 Jan;34(1):72-83. doi: 10.1016/j.semnephrol.2013.11.010. Epub 2013 Nov 22.
Chaperone-mediated autophagy (CMA) is a lysosomal proteolytic pathway in which cytosolic substrate proteins contain specific chaperone recognition sequences required for degradation and are translocated directly across the lysosomal membrane for destruction. CMA proteolytic activity has a reciprocal relationship with macroautophagy: CMA is most active in cells in which macroautophagy is least active. Normal renal proximal tubular cells have low levels of macroautophagy, but high basal levels of CMA activity. CMA activity is regulated by starvation, growth factors, oxidative stress, lipids, aging, and retinoic acid signaling. The physiological consequences of changes in CMA activity depend on the substrate proteins present in a given cell type. In the proximal tubule, increased CMA results from protein or calorie starvation and from oxidative stress. Overactivity of CMA can be associated with tubular lysosomal pathology and certain cancers. Reduced CMA activity contributes to protein accumulation in renal tubular hypertrophy, but may contribute to oxidative tissue damage in diabetes and aging. Although there are more questions than answers about the role of high basal CMA activity, this remarkable feature of tubular protein metabolism appears to influence a variety of chronic diseases.
伴侣介导的自噬（CMA）是一种溶酶体蛋白水解途径，其中胞质底物蛋白含有降解所需的特定伴侣识别序列，并直接穿过溶酶体膜进行降解。CMA蛋白水解活性与巨自噬呈反比关系：CMA在巨自噬活性最低的细胞中最活跃。正常肾近端小管细胞的巨自噬水平较低，但CMA活性的基础水平较高。CMA活性受饥饿、生长因子、氧化应激、脂质、衰老和视黄酸信号调节。CMA活性变化的生理后果取决于特定细胞类型中存在的底物蛋白。在近端小管中，CMA增加是由蛋白质或热量饥饿以及氧化应激引起的。CMA活性过高可能与肾小管溶酶体病理和某些癌症有关。CMA活性降低导致肾小管肥大中蛋白质积累，但可能导致糖尿病和衰老中的氧化组织损伤。尽管关于高基础CMA活性的作用问题多于答案，但肾小管蛋白质代谢的这一显著特征似乎会影响多种慢性疾病。
