mTOR regulation of autophagy

Abstract 

Nutrient starvation induces autophagy in eukaryotic cells through inhibition of TOR (target of rapamycin), an evolutionarily-conserved protein kinase. TOR, as a central regulator of cell growth, plays a key role at the interface of the pathways that coordinately regulate the balance between cell growth and autophagy in response to nutritional status, growth factor and stress signals. Although TOR has been known as a key regulator of autophagy for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This review discusses the recent advances in understanding of the mechanism by which TOR regulates autophagy with focus on mammalian TOR (mTOR) and its regulation of the autophagy machinery.

Abbreviations: mTOR, mammalian target of rapamycin, mTORC1, mTOR complex 1, mTORC2, mTOR complex 2, raptor, regulatory associated protein of mTOR, rictor, rapamycin insensitive companion of mTOR, Atg, Autophagy-related gene, TSC, tuberous sclerosis complex, Rheb, ras homolog enriched in brain, PKB, protein kinase B, GAP1, general amino acid permease 1, AMPK, 5′-AMP-activated protein kinase, hVps34, human ortholog of yeast vacuolar protein sorting 34, ULK1, UNC-51-like kinase 1, ULK2, UNC-51-like kinase 2, FIP200, focal adhesion kinase (FAK) family interacting protein of 200kDa, GATE-16, Golgi-associated ATPase enhancer of 16kDa, GABARAP, γ-aminobutyric acid (GABA) receptor associated protein, TGN, trans-Golgi network

Keywords: Mammalian target of rapamycin, Autophagy-related gene 1, UNC-51-like kinase 1, UNC-51-like kinase 2, Autophagy-related gene 13