Autophagy in acute kidney injury

Abstract

Autophagy is a conserved multistep pathway that degrades and recycles damaged organelles and macromolecules to maintain intracellular homeostasis. The autophagy pathway is upregulated under stress conditions including cell starvation, hypoxia, nutrient and growth-factor deprivation, ER stress, and oxidant injury, most of which are involved in the pathogenesis of acute kidney injury (AKI). Recent studies demonstrate that basal autophagy in the kidney is vital for the normal homeostasis of the proximal tubules. Deletion of key autophagy proteins impaired renal function and increased p62 levels and oxidative stress. In models of AKI, autophagy deletion in proximal tubules worsened tubular injury and renal function, highlighting that autophagy is renoprotective in models of AKI. In addition to nonselective sequestration of autophagic cargo, autophagy can facilitate selective degradation of damaged organelles particularly mitochondrial degradation through the process of mitophagy. Damaged mitochondria accumulate in autophagy-deficient kidneys of mice subjected to ischemia-reperfusion injury, but the precise mechanisms of regulation of mitophagy in AKI are not yet elucidated. Recent progress in identifying the interplay of autophagy, apoptosis, and regulated necrosis has revived interest in examining shared pathways/molecules in this crosstalk during the pathogenesis of AKI. Autophagy and its associated pathways pose potentially unique targets for therapeutic interventions in AKI.

Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury

“…Mitophagy, one type of autophagy, is known as selective removal of damaged and depolarized mitochondria. Although initially identified in familial Parkinson’s disease [40], recent studies showed that autophagy in kidney was of great significance for the homeostasis of renal tubular [41, 42]. Autophagy and mitophagy have been well studied in renal ischemia-reperfusion, sepsis and cisplatin induced acute kidney injury [15, 43-45].…”

Autophagy in kidney disease and aging: lessons from rodent models

“…36,[190][191][192][193][194][195][196][197][198][199][200][201][202][203] An in-depth review of the relationship between autophagy and AKI has been published in this journal. 204 Autophagy in renal fibrosis. Unilateral ureteral obstruction (UUO) in rodents has been established as a classic model of progressive renal fibrosis.…”

Inhibition of Autophagy Attenuated Ethylene Glycol Induced Crystals Deposition and Renal Injury in a Rat Model of Nephrolithiasis

“…Growing evidence suggests that autophagy is involved in physiological processes as well as in pathogenesis of many kidney diseases [8, 9]. Autophagy is a highly conservative regulatory system in which intracellular damaged organelles and protein aggregates are removed via the lysosomal degradation pathway [10, 11].…”