Autophagy Mechanisms in Renal Injury and Repair

Autophagy is an evolutionarily conserved process by which cells degrade and recycle damaged organelles and macromolecules through lysosome-mediated pathways. In the kidney, basal autophagy maintains tubular epithelial homeostasis by clearing dysfunctional mitochondria, limiting oxidative stress and preventing maladaptive inflammation. Following acute insults such as ischaemia–reperfusion or toxin exposure, an early upregulation of autophagy protects proximal tubule cells from apoptosis, supports energy balance and facilitates removal of protein aggregates. During the transition to repair, dynamic regulation of key autophagy genes ensures proper clearance of profibrotic mediators and promotes tissue regeneration. In chronic settings, defective or insufficient autophagy contributes to persistent tubular injury, interstitial fibrosis and progression to end-stage renal disease. Central regulators include the nutrient sensor mTORC1, the energy sensor AMPK and the transcription factor TFEB, which coordinate autophagosome formation, lysosomal biogenesis and cargo selection. Therapeutic modulation of these pathways offers promise in attenuating both acute and chronic kidney injury by restoring autophagic flux and re-establishing cellular homeostasis.

Research from Nature Portfolio

Foundational studies have revealed that pharmacological activation of AMPKα triggers renal autophagy and markedly reduces tubular cell apoptosis in models of cisplatin-induced acute kidney injury, highlighting a cytoprotective mechanism that limits nephrotoxic damage. In sepsis-associated endotoxaemia, induction of autophagy in tubular epithelium preserves kidney function by facilitating the clearance of damaged organelles and suppressing inflammatory cascades; genetic ablation or chemical inhibition of core autophagy genes exacerbates injury, underscoring the renoprotective role of this pathway.

Autophagy Mechanisms in Renal Injury and Repair publication trend

The graph below shows the total number of articles in autophagy mechanisms in renal injury and repair across all publications each year (not limited to Nature Index journals).

Technical terms

Autophagy: A cellular degradation process that delivers damaged or surplus cytoplasmic components to lysosomes for recycling.

mTORC1: A nutrient-sensing kinase complex that inhibits autophagy when nutrients are abundant.

AMPK: An energy-sensing kinase that activates autophagy under conditions of cellular stress or low ATP.

TFEB: A transcription factor that regulates genes involved in lysosome biogenesis and autophagosome formation.

Autophagic flux: The dynamic process of autophagosome formation, cargo degradation and lysosomal turnover.

Epithelial–mesenchymal transition: A programme by which epithelial cells acquire mesenchymal features, contributing to fibrosis.

Inflammasome: A multiprotein complex that senses cellular stress and triggers proinflammatory cytokine maturation.

References

1. Dynamic regulation of proximal tubular autophagy from injury to repair after ischemic kidney damage. Cellular & Molecular Biology Letters (2024).
2. Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis. Cell Death & Disease (2023).
3. Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPKα-regulated Autophagy Induction. Scientific Reports (2016).
4. Autophagy is activated to protect against endotoxic acute kidney injury. Scientific Reports (2016).
5. Autophagy attenuates tubulointerstital fibrosis through regulating transforming growth factor-β and NLRP3 inflammasome signaling pathway. Cell Death & Disease (2019).