Kidney Diseases (May 2021)

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury

  • Xiao-cui Chen,
  • Zhi-hang Li,
  • Chen Yang,
  • Ji-xin Tang,
  • Hui-yao Lan,
  • Hua-feng Liu

DOI
https://doi.org/10.1159/000515035
Journal volume & issue
Vol. 7, no. 4
pp. 254 – 267

Abstract

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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.

Keywords