title: [Reparative autophagy and autophagy death of cells. Functional and regulatory aspects].
abstract: Molecular regulation of reparative/homeostatic autophagy induced by failure of vital resources and by cellular stress is considered. Extensive autophagy regulatory apparatus responds to starvation, insufficiency of growth factors and energy supply, accumulation of unfolded proteins (ER stress), reactive oxygen species, microbial invasion. Central sensor of the regulation is kinase mTOR. Part of the mTOR pool presented in lysosomes responds to the local level of amino acids and is able to induce autophagy under low rates of intralysosomal proteolysis. Autophagy is a self-regulated cell process, the peak of autophagy is followed by its regulatory weakening by amino acids formed in autophagolysosomes. Protective effect of autophagy is associated mainly with removal of permeabilized mitochondria generating ROS, and elimination of abnormally folded proteins. Autophagy has optimum of its activity: its deficiency leads to accelerated cellular aging, and the excessive autophagy brings to the deficiency of cellular survival resources and cell death. Autophagy cell death seems like a hyper-stimulated self-eating of the cell, but more probably that excessive autophagy disturbs cellular energy supply and switches on some specific cell death signalization (possibly associated with kinases c-Jun, DRP-1, PI3K class I etc.). Some approaches to use reparative autophagy for prevention of cell degeneration are considered.
authors.forename: A B
authors.initials: AB
authors.lastname: Pupyshev
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D064550:Death-Associated Protein Kinases / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D056811:Unfolded Protein Response
chemical_list: D064550:Death-Associated Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases