Autophagy in Chronic Kidney Diseases

Abstract

Background: Autophagy is the degrading process of protein and organelles mediated by lysosomes. This process is involved in purging senescent organelles and subversive proteins while maintaining the stability of the intracellular environment. This phenomenon is highly conservative, existing in nearly every species, and is involved in cell growth, proliferation and tumorigenesis.

Summary: In recent decades, with the discovery of autophagy-related genes and proteins in conjunction with the improvement in detection methods, the study of autophagy is constantly achieving new breakthroughs. It has been discovered that multiple regulatory mechanisms, including Atg protein and its conjugation system, mammalian target of rapamycin upstream and downstream pathways, complex of B-cell lymphoma-2 and Beclin-1c, cellular stress and dual regulation of p53 protein, jointly mediate the process of autophagy. Aberrant autophagy can cause impairment of resident kidney cells and development of various renal diseases.

Key message: In this paper, we summarize recent discoveries regarding the development and regulatory mechanisms of autophagy. We also highlight the role of autophagy in the pathogenesis of some kidney diseases, such as diabetic nephropathy, obstructive nephropathy, IgA nephropathy, nephropathic cystinosis, aristolochic acid nephropathy, autoimmune kidney diseases and chronic cyclosporin A-induced nephrotoxicity. These findings provide new insights into the mechanisms of renal diseases and are useful for designing novel therapeutic approaches for the treatment of chronic kidney disease.

Keywords: Autophagy; Autophagy-related genes or proteins; Chronic kidney diseases; Mammalian target of rapamycin; Regulatory mechanisms.

Fig. 1

Regulatory mechanisms of autophagy. PI3K-I = Phosphatidylinositol 3-kinase I; Akt/PKB = protein kinase B; TSC = tuberous sclerosis complex; Rheb = Ras homologue enriched in brain; GΒL = G protein β-like; AMPK = AMP-activated protein kinase; HIF-1 = hypoxia-inducible factor-1; BNIP3 = Bcl-2/E1B 19 kDa-interacting protein 3; JNK1 = c-Jun n-terminal kinase 1; IRE1 = inositol-requiring enzyme 1; PERK = PKR-like endoplasmic reticulum kinase; eIF2α = eukaryotic initiation factor 2α; Bcl-2 = B-cell lymphoma-2; S6K1 = subunit 6 kinase 1; 4EBP1 = eIF4E-binding protein 1; ULK = Unc-51-like kinase.