Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, School of Pharmaceutical Sciences, and Medical Research Institute, Wuhan University, Wuhan, Hubei, 430072, China; Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, China; Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
Trends Cell Biol. 2017 Jul;27(7):491-504. doi: 10.1016/j.tcb.2017.01.001. Epub 2017 Feb 3.
Previously thought of as a nonselective digestion process, autophagy is now known to specifically degrade aggregated proteins and damaged cellular organelles through the action of autophagy receptors, which provides cellular quality control and maintains homeostasis. Autophagy receptors recognize and recruit specific cargoes to the autophagosome-lysosome pathway for degradation in ubiquitin-dependent and -independent manners, and their functions (in selective autophagy) are regulated by protein modifications, for example, phosphorylation and ubiquitination. Growing evidence has linked the genetic variants of autophagy receptors to neurodegenerative diseases and multiple experimental systems have validated their roles in modulating the disease process. Here, we review the recent advances in understanding the physiology and pathophysiology of autophagy receptors in selective autophagy, and discuss their potentials as therapeutic targets for neurodegenerative diseases.
先前被认为是一种非选择性的消化过程,自噬现在被认为通过自噬受体的作用特异性降解聚集的蛋白质和受损的细胞细胞器,为细胞提供质量控制并维持体内平衡。自噬受体通过泛素依赖性和非依赖性方式识别和招募特定货物到自噬体溶酶体途径进行降解,其功能(在选择性自噬中)受蛋白修饰(例如磷酸化和泛素化)调节。越来越多的证据将自噬受体的遗传变异与神经退行性疾病联系起来,并且多个实验系统已经验证了它们在调节疾病过程中的作用。在这里,我们综述了近年来对选择性自噬中自噬受体的生理学和病理生理学的理解进展,并讨论了它们作为神经退行性疾病治疗靶点的潜力。