Mechanisms and biological functions of autophagy in diseased and ageing kidneys.
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.
Departments of Medicine, Microbiology and Immunology, The Research Institute of the McGill University Health Center, 2155 Guy Street, Montreal, QC H3H 2R9, Canada.
Sophie
S
Fougeray
Service de Biochimie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 20 Rue Leblanc, 75015 Paris, France.
Nicolas
N
Pallet
D000375:Aging / Q000378:metabolism*; D017209:Apoptosis; D001343:Autophagy / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism