溶酶体耗竭引发的自噬损伤在进行性肾损伤中的作用
Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury.
作者信息
Chen Xiao-Cui, Li Zhi-Hang, Yang Chen, Tang Ji-Xin, Lan Hui-Yao, Liu Hua-Feng
机构信息
Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
出版信息
Kidney Dis (Basel). 2021 Jul;7(4):254-267. doi: 10.1159/000515035. Epub 2021 May 25.
BACKGROUND
Macroautophagy (autophagy) is a cellular recycling process involving the destruction of damaged organelles and proteins in intracellular lysosomes for efficient nutrient reuse.
SUMMARY
Impairment of the autophagy-lysosome pathway is tightly associated with multiple kidney diseases, such as diabetic nephropathy, proteinuric kidney disease, acute kidney injury, crystalline nephropathy, and drug- and heavy metal-induced renal injury. The impairment in the process of autophagic clearance may induce injury in renal intrinsic cells by activating the inflammasome, inducing cell cycle arrest, and cell death. The lysosome depletion may be a key mechanism triggering this process. In this review, we discuss this pathway and summarize the protective mechanisms for restoration of lysosome function and autophagic flux via the endosomal sorting complex required for transport (ESCRT) machinery, lysophagy, and transcription factor EB-mediated lysosome biogenesis.
KEY MESSAGE
Further exploring mechanisms of ESCRT, lysophagy, and lysosome biogenesis may provide novel therapy strategies for the management of kidney diseases.
背景
巨自噬（自噬）是一种细胞循环过程，涉及在细胞内溶酶体中破坏受损细胞器和蛋白质以实现有效的营养物质再利用。
总结
自噬-溶酶体途径的损伤与多种肾脏疾病密切相关，如糖尿病肾病、蛋白尿性肾病、急性肾损伤、结晶性肾病以及药物和重金属诱导的肾损伤。自噬清除过程中的损伤可能通过激活炎性小体、诱导细胞周期停滞和细胞死亡来诱导肾固有细胞损伤。溶酶体耗竭可能是触发这一过程的关键机制。在本综述中，我们讨论了这一途径，并总结了通过运输所需的内体分选复合体（ESCRT）机制、溶酶体自噬和转录因子EB介导的溶酶体生物发生来恢复溶酶体功能和自噬通量的保护机制。
关键信息
进一步探索ESCRT、溶酶体自噬和溶酶体生物发生的机制可能为肾脏疾病的治疗提供新的策略。
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