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Mechanisms and biological functions of autophagy in diseased and ageing kidneys

Nature Reviews Nephrology volume 11, pages 34–45 (2015)Cite this article

Subjects

Key Points

  • Autophagy is a lysosomal-mediated process that degrades cytoplasmic components

  • Autophagy involves the formation and degradation of double-membrane-limited vesicles called autophagosomes

  • The main activators of autophagic flux are immune stimuli and starvation

  • Autophagy promotes cytoprotection by inhibiting apoptosis, inflammation and oxidative stress

  • Autophagy is renoprotective in numerous models of acute kidney injury, glomerular disease and ageing

  • The importance of autophagy in the pathophysiology of human renal disease remains to be determined

Abstract

Autophagy degrades pathogens, altered organelles and protein aggregates, and is characterized by the sequestration of cytoplasmic cargos within double-membrane-limited vesicles called autophagosomes. The process is regulated by inputs from the cellular microenvironment, and is activated in response to nutrient scarcity and immune triggers, which signal through a complex molecular network. Activation of autophagy leads to the formation of an isolation membrane, recognition of cytoplasmic cargos, expansion of the autophagosomal membrane, fusion with lysosomes and degradation of the autophagosome and its contents. Autophagy maintains cellular homeostasis during stressful conditions, dampens inflammation and shapes adaptive immunity. A growing body of evidence has implicated autophagy in kidney health, ageing and disease; it modulates tissue responses during acute kidney injuries, regulates podocyte homeostasis and protects against age-related renal disorders. The renoprotective functions of autophagy in epithelial renal cells and podocytes are mostly mediated by the clearance of altered mitochondria, which can activate inflammasomes and apoptosis, and the removal of protein aggregates, which might trigger inflammation and cell death. In translational terms, autophagy is undoubtedly an attractive target for developing new renoprotective treatments and identifying markers of kidney injury.

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Figure 1: The molecular biology of autophagy.
Figure 2: The process of mitophagy.
Figure 3: Immune and metabolic signals regulate autophagy.
Figure 4: Putative cytoprotective functions of autophagy in tubular cells and podocytes.

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Authors and Affiliations

  1. Departments of Medicine, Microbiology and Immunology, The Research Institute of the McGill University Health Center, 2155 Guy Street, Montreal, H3H 2R9, QC, Canada

    Sophie Fougeray

  2. Service de Biochimie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 20 Rue Leblanc, Paris, 75015, France

    Nicolas Pallet

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Both authors researched the data, discussed the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Fougeray, S., Pallet, N. Mechanisms and biological functions of autophagy in diseased and ageing kidneys. Nat Rev Nephrol 11, 34–45 (2015). https://doi.org/10.1038/nrneph.2014.201

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