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Review
. 2021 Jul;7(4):254-267.
doi: 10.1159/000515035. Epub 2021 May 25.

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury

Xiao-Cui Chen  1 , Zhi-Hang Li  1 , Chen Yang  1 , Ji-Xin Tang  1 , Hui-Yao Lan  2 , Hua-Feng Liu  1
Affiliations
Review

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury

Xiao-Cui Chen et al. Kidney Dis (Basel). 2021 Jul.

Abstract

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: Autophagy; Kidney disease; Lysosome; Podocyte; Tubular epithelial cell.

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Conflict of interest statement

No potential conflicts of interest were disclosed.

Figures

Fig. 1
Fig. 1
Potential mechanisms of renal injury triggered by lysosome depletion in kidney diseases. Lysosome rupture that causes lysosomal dysfunction and the release of endogenous hydrolytic enzymes, leading to the disruption of autophagic flux and LMP, which further triggers ROS production, NLRP3 inflammasome activation, cell cycle arrest, and RIPK1/RIPK3/phospho-MLKL-mediated necroptosis in renal intrinsic cells, consequently promoting renal fibrosis and injury. LC3, microtubule-associated protein 1 light chain 3; LMP, lysosomal membrane permeabilization; ROS, reactive oxygen species; IL-1β, interleukin-1β; IL-18, interleukin-18.
Fig. 2
Fig. 2
Overview of potential protective mechanisms for coping with the lysosome depletion. Different repair mechanisms have been discovered to restore the function of lysosome depending on the extent of lysosomal damage, mainly through 3 potential mechanisms: the rescue of slightly damaged lysosomes mediated by ESCRT machinery, the removal of severely damaged lysosomes via lysophagy, and lysosome biogenesis regulated by TFEB that coordinately replenish intact lysosomes for restoring lysosome function and improving autophagic clearance, which may provide a potential therapy strategies for the management of kidney diseases. ESCRT, the endosomal sorting complex required for transport; mTOR, mammalian target of rapamycin; AMPK, AMP-activated protein kinase; TFEB, transcription factor EB.
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References

    1. Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature. 2008 Feb 28;451((7182)):1069–75. - PMC - PubMed
    1. Murrow L, Debnath J. Autophagy as a stress-response and quality-control mechanism: implications for cell injury and human disease. Annu Rev Pathol. 2013 Jan 24;8:105–37. - PMC - PubMed
    1. Pyo JO, Nah J, Jung YK. Molecules and their functions in autophagy. Exp Mol Med. 2012 Feb 29;44((2)):73–80. - PMC - PubMed
    1. Sureshbabu A, Ryter SW, Choi ME. Oxidative stress and autophagy: crucial modulators of kidney injury. Redox Biol. 2015;4:208–14. - PMC - PubMed
    1. Zhang L, Sheng R, Qin Z. The lysosome and neurodegenerative diseases. Acta Biochim Biophys Sin. 2009 Jun;41((6)):437–45. - PubMed