title: Coordinate regulation of autophagy and the ubiquitin proteasome system by MTOR.
abstract: Proteins in eukaryotic cells are continually being degraded to amino acids either by the ubiquitin proteasome system (UPS) or by the autophagic-lysosomal pathway. The breakdown of proteins by these 2 degradative pathways involves totally different enzymes that function in distinct subcellular compartments. While most studies of the UPS have focused on the selective ubiquitination and breakdown of specific cell proteins, macroautophagy/autophagy is a more global nonselective process. Consequently, the UPS and autophagy were traditionally assumed to serve distinct physiological functions and to be regulated in quite different manners. However, recent findings indicate that protein breakdown by these 2 systems is coordinately regulated by important physiological stimuli. The activation of MTORC1 by nutrients and hormones rapidly suppresses proteolysis by both proteasomes and autophagy, which helps promote protein accumulation, whereas in nutrient-poor conditions, MTORC1 inactivation causes the simultaneous activation of these 2 degradative pathways to supply the deprived cells with a source of amino acids. Also this selective breakdown of key anabolic proteins by the UPS upon MTORC1 inhibition can help limit growth-related processes (e.g., cholesterol biosynthesis). Thus, the collaboration of these 2 degradative systems, together with the simultaneous control of protein translation by MTORC1, provide clear advantages to the organism in both growth and starvation conditions.
authors.affiliation: a Department of Cell Biology , Harvard Medical School , Boston , MA , USA.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Zhao
authors.affiliation: a Department of Cell Biology , Harvard Medical School , Boston , MA , USA.
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017510:Protein Folding; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D025801:Ubiquitin; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex
keywords: MTOR; autophagy; proteasomes; ubiquitination