Regulation of Autophagy through TORC1 and mTORC1

Schoenheimer, R. (1942). The Dynamic State of Body Constituents, Harvard University Press.

Ashoford, 1962, Cytoplasmic components in hepatic cell lysosomes, J. Cell Biol., 12, 198, 10.1083/jcb.12.1.198

Tsukada, 1993, Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae, FEBS Lett., 333, 169, 10.1016/0014-5793(93)80398-E

Thumm, 1994, Isolation of Autophagocytosis Mutants of Saccharomyces cerevisiae, FEBS Lett., 349, 275, 10.1016/0014-5793(94)00672-5

Harding, 1995, Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway, J. Cell Biol., 131, 591, 10.1083/jcb.131.3.591

Blommaart, 1995, Phosphorylation of Ribosomal-Protein S6 Is Inhibitory for Autophagy in Isolated Rat Hepatocytes, J. Biol. Chem., 270, 2320, 10.1074/jbc.270.5.2320

Noda, 1998, Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast, J. Biol. Chem., 273, 3963, 10.1074/jbc.273.7.3963

Guo, 2016, Autophagy, Metabolism, and Cancer, Cold Spring Harb. Symp. Quant. Biol., 81, 73, 10.1101/sqb.2016.81.030981

Funakoshi, 1997, Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae, Gene, 192, 207, 10.1016/S0378-1119(97)00031-0

Kamada, 2000, Tor-mediated induction of autophagy via an Apg1 protein kinase complex, J. Cell Biol., 150, 1507, 10.1083/jcb.150.6.1507

Kamada, 2010, Tor directly controls the Atg1 kinase complex to regulate autophagy, Mol. Cell. Biol., 30, 1049, 10.1128/MCB.01344-09

Yeasmin, A.M., Waliullah, T.M., Kondo, A., Kaneko, A., Koike, N., and Ushimaru, T. (2016). Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylation and Promotes Autophagy after the Inactivation of TORC1. PLoS ONE, 11.

Stephan, 2009, The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy, Proc. Natl. Acad. Sci. USA, 106, 17049, 10.1073/pnas.0903316106

Fujioka, 2014, Structural basis of starvation-induced assembly of the autophagy initiation complex, Nat. Struct. Mol. Biol., 21, 513, 10.1038/nsmb.2822

Yamamoto, 2016, The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes, Dev. Cell, 38, 86, 10.1016/j.devcel.2016.06.015

Kabeya, 2009, Characterization of the Atg17–Atg29–Atg31 complex specifically required for starvation-induced autophagy in Saccharomyces cerevisiae, Biochem. Biophys. Res. Commun., 389, 612, 10.1016/j.bbrc.2009.09.034

Ragusa, 2012, Architecture of the Atg17 Complex as a Scaffold for Autophagosome Biogenesis, Cell, 151, 1501, 10.1016/j.cell.2012.11.028

Matsuura, 1997, Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae, Gene, 192, 245, 10.1016/S0378-1119(97)00084-X

Yeh, 2011, An Atg13 protein-mediated self-association of the Atg1 protein kinase is important for the induction of autophagy, J. Biol. Chem., 286, 28931, 10.1074/jbc.M111.250324

Suzuki, 2001, The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation, EMBO J., 20, 5971, 10.1093/emboj/20.21.5971

Suzuki, 2007, Hierarchy of Atg proteins in pre-autophagosomal structure organization, Genes Cells, 12, 209, 10.1111/j.1365-2443.2007.01050.x

Ueno, 1999, Autolysosomal membrane-associated betaine homocysteine methyltransferase. Limited degradation fragment of a sequestered cytosolic enzyme monitoring autophagy, J. Biol. Chem., 274, 15222, 10.1074/jbc.274.21.15222

Yan, 1998, Identification of mouse ULK1, a novel protein kinase structurally related to C. elegans UNC-51, Biochem. Biophys. Res. Commun., 246, 222, 10.1006/bbrc.1998.8546

Hosokawa, 2009, Nutrient-dependent mTORC1 association with the ULK1–Atg13–FIP200 complex required for autophagy, Mol. Biol. Cell, 20, 1981, 10.1091/mbc.e08-12-1248

Jung, 2009, ULK–Atg13–FIP200 complexes mediate mTOR signaling to the autophagy machinery, Mol. Biol. Cell, 20, 1992, 10.1091/mbc.e08-12-1249

Chan, 2009, Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism, Mol. Cell. Biol., 29, 157, 10.1128/MCB.01082-08

Hara, 2008, FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells, J. Cell Biol., 181, 497, 10.1083/jcb.200712064

Mercer, 2009, A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy, Autophagy, 5, 649, 10.4161/auto.5.5.8249

Hosokawa, 2009, Atg101, a novel mammalian autophagy protein interacting with Atg13, Autophagy, 5, 973, 10.4161/auto.5.7.9296

Itakura, 2010, Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins, Autophagy, 6, 764, 10.4161/auto.6.6.12709

Papinski, 2014, Early Steps in Autophagy Depend on Direct Phosphorylation of Atg9 by the Atg1 Kinase, Mol. Cell, 53, 471, 10.1016/j.molcel.2013.12.011

Noda, 2000, Apg9p/Cvt7p is an integral membrane protein required for transport vesicle formation in the Cvt and autophagy pathways, J. Cell Biol., 148, 465, 10.1083/jcb.148.3.465

Reggiori, 2004, The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure, Dev. Cell, 6, 79, 10.1016/S1534-5807(03)00402-7

Kira, 2013, TRAPPIII is responsible for vesicular transport from early endosomes to Golgi, facilitating Atg9 cycling in autophagy, J. Cell Sci., 126, 4963

Yamamoto, 2012, Atg9 vesicles are an important membrane source during early steps of autophagosome formation, J. Cell Biol., 198, 219, 10.1083/jcb.201202061

Suzuki, 2015, Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation, Proc. Natl. Acad. Sci. USA, 112, 3350, 10.1073/pnas.1421092112

Rao, 2016, The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy, Nat. Commun., 7, 10338, 10.1038/ncomms10338

Karanasios, 2016, Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles, Nat. Commun., 7, 1, 10.1038/ncomms12420

Mizushima, 2011, The Role of Atg Proteins in Autophagosome Formation, Annu. Rev. Cell Dev. Biol., 27, 107, 10.1146/annurev-cellbio-092910-154005

Yin, 2016, Autophagy: Machinery and regulation, Microb. Cell, 3, 588, 10.15698/mic2016.12.546

Sturgill, 2008, TOR1 and TOR2 have distinct locations in live cells, Eukaryotic Cell, 7, 1819, 10.1128/EC.00088-08

Dubouloz, 2005, The TOR and EGO protein complexes orchestrate microautophagy in yeast, Mol. Cell, 19, 15, 10.1016/j.molcel.2005.05.020

Kira, 2015, Dynamic relocation of the TORC1–Gtr1/2–Ego1/2/3 complex is regulated by Gtr1 and Gtr2, Mol. Biol. Cell, 27, 382, 10.1091/mbc.e15-07-0470

Powis, 2015, Crystal structure of the Ego1–Ego2–Ego3 complex and its role in promoting Rag GTPase-dependent TORC1 signaling, Cell Res., 25, 1043, 10.1038/cr.2015.86

Jeong, 2012, Crystal Structure of the Gtr1pGTP-Gtr2pGDP Protein Complex Reveals Large Structural Rearrangements Triggered by GTP-to-GDP Conversion, J. Biol. Chem., 287, 29648, 10.1074/jbc.C112.384420

Binda, 2009, The Vam6 GEF controls TORC1 by activating the EGO complex, Mol. Cell, 35, 563, 10.1016/j.molcel.2009.06.033

Kira, 2014, Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2–Npr3 inactivates TORC1 and induces autophagy, Autophagy, 10, 1565, 10.4161/auto.29397

Ukai, H., Araki, Y., Kira, S., and Noda, T. (2017). Osaka University, Osaka, Japan, Unpublished work.

Sabatini, 2014, Regulation of mTORC1 by amino acids, Trends Cell Biol., 24, 400, 10.1016/j.tcb.2014.03.003

Ichimura, 2000, A ubiquitin-like system mediates protein lipidation, Nature, 408, 488, 10.1038/35044114

Kirisako, 1999, Formation process of autophagosome is traced with Apg8/Aut7p in yeast, J. Cell Biol., 147, 435, 10.1083/jcb.147.2.435

Huang, 2000, The itinerary of a vesicle component, Aut7p/Cvt5p, terminates in the yeast vacuole via the autophagy/Cvt pathways, J. Biol. Chem., 275, 5845, 10.1074/jbc.275.8.5845

Abeliovich, 2000, Dissection of autophagosome biogenesis into distinct nucleation and expansion steps, J. Cell Biol., 151, 1025, 10.1083/jcb.151.5.1025

Nakatogawa, 2007, Atg8, a Ubiquitin-like Protein Required for Autophagosome Formation, Mediates Membrane Tethering and Hemifusion, Cell, 130, 165, 10.1016/j.cell.2007.05.021

Bernard, 2015, Rph1/KDM4 Mediates Nutrient-Limitation Signaling that Leads to the Transcriptional Induction of Autophagy, Curr. Biol., 25, 546, 10.1016/j.cub.2014.12.049

Yu, 2015, The yeast chromatin remodeler Rsc1–RSC complex is required for transcriptional activation of autophagy-related genes and inhibition of the TORC1 pathway in response to nitrogen starvation, Biochem. Biophys. Res. Commun., 464, 1248, 10.1016/j.bbrc.2015.07.114

Bartholomew, 2012, Ume6 transcription factor is part of a signaling cascade that regulates autophagy, Proc. Natl. Acad. Sci. USA, 109, 11206, 10.1073/pnas.1200313109

Yang, 2010, Positive or negative roles of different cyclin-dependent kinase Pho85–cyclin complexes orchestrate induction of autophagy in Saccharomyces cerevisiae, Mol. Cell, 38, 250, 10.1016/j.molcel.2010.02.033

Umekawa, 2012, Ksp1 kinase regulates autophagy via the target of rapamycin complex 1 (TORC1) pathway, J. Biol. Chem., 287, 16300, 10.1074/jbc.M112.344952

Hu, 2015, A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation regulates autophagy, Nat. Cell Biol., 17, 930, 10.1038/ncb3189

Coffman, 1997, Nitrogen GATA factors participate in transcriptional regulation of vacuolar protease genes in Saccharomyces cerevisiae, J. Bacteriol., 179, 5609, 10.1128/jb.179.17.5609-5613.1997

Kulkarni, 2001, Gln3p nuclear localization and interaction with Ure2p in Saccharomyces cerevisiae, J. Biol. Chem., 276, 32136, 10.1074/jbc.M104580200

Cooper, 2002, Transmitting the signal of excess nitrogen in Saccharomyces cerevisiae from the Tor proteins to the GATA factors: Connecting the dots, FEMS Microbiol. Rev., 26, 223, 10.1111/j.1574-6976.2002.tb00612.x

Chan, 2001, Regulation of APG14 expression by the GATA-type transcription factor Gln3p, J. Biol. Chem., 276, 6463, 10.1074/jbc.M008162200

Tate, 2017, General Amino Acid Control and 14-3-3 Proteins Bmh1/2 Are Required for Nitrogen Catabolite Repression-Sensitive Regulation of Gln3 and Gat1 Localization, Genetics, 205, 633, 10.1534/genetics.116.195800

Kamada, 2017, Novel tRNA function in amino acid sensing of yeast Tor complex1, Genes Cells, 22, 135, 10.1111/gtc.12462

Sardiello, 2009, A Gene Network Regulating Lysosomal Biogenesis and Function, Science, 325, 473, 10.1126/science.1174447

Settembre, 2011, TFEB links autophagy to lysosomal biogenesis, Science, 332, 1429, 10.1126/science.1204592

Kihara, 2001, Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae, J. Cell Biol., 152, 519, 10.1083/jcb.152.3.519

Itakura, 2008, Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG, Mol. Biol. Cell, 19, 5360, 10.1091/mbc.e08-01-0080

Matsunaga, 2009, Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages, Nat. Cell Biol., 11, 385, 10.1038/ncb1846

Russell, 2013, ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase, Nat. Cell Biol., 15, 741, 10.1038/ncb2757

Hamasaki, 2010, Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy, Traffic, 11, 468, 10.1111/j.1600-0854.2010.01034.x

Hao, 2016, The PtdIns3-phosphatase MTMR3 interacts with mTORC1 and suppresses its activity, FEBS Lett., 590, 161, 10.1002/1873-3468.12048

Nobukuni, 2007, hvps34, an ancient player, enters a growing game: mTOR Complex1/S6K1 signaling, Curr. Opin. Cell Biol., 19, 135, 10.1016/j.ceb.2007.02.019

Shigemitsu, 1999, Regulation of translational effectors by amino acid and mammalian target of rapamycin signaling pathways. Possible involvement of autophagy in cultured hepatoma cells, J. Biol. Chem., 274, 1058, 10.1074/jbc.274.2.1058