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.
Key words: autophagy, cellular stress, autophagosomes, autophagolysosomes, lysosomes, cell survival, cell death
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