Nutrient-sensing mTORC1: Integration of metabolic and autophagic signals.

PubWeight™: 0.84‹?›

🔗 View Article (PMID 26773603)

Published in J Mol Cell Cardiol on January 07, 2016

Authors

Valerie P Tan1, Shigeki Miyamoto2

Author Affiliations

1: Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.
2: Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA. Electronic address: smiyamoto@ucsd.edu.

Articles cited by this

(truncated to the top 100)

Autophagy in the pathogenesis of disease. Cell (2008) 34.68

Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature (1996) 26.30

TSC2 mediates cellular energy response to control cell growth and survival. Cell (2003) 20.21

mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell (2002) 18.22

Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell (2005) 17.81

Functions of lysosomes. Annu Rev Physiol (1966) 17.76

TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol (2002) 17.41

AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell (2008) 16.72

The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet (1963) 16.71

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol (2011) 15.71

The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science (2008) 14.08

Autophagy regulates lipid metabolism. Nature (2009) 13.33

Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell (2010) 12.24

TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell (2006) 11.85

Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell (2002) 11.50

Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science (2010) 11.29

PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell (2007) 9.68

Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J (2007) 9.65

Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem (1998) 9.37

ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell (2009) 9.24

Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell (2009) 9.14

Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol (2008) 8.92

TFEB links autophagy to lysosomal biogenesis. Science (2011) 8.87

The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nat Med (2007) 8.82

Potential therapeutic applications of autophagy. Nat Rev Drug Discov (2007) 8.56

Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res (2007) 8.44

Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol (2003) 8.25

Autophagy and metabolism. Science (2010) 8.10

Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell (2005) 7.75

Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell (2010) 7.61

Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell (2010) 7.59

mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science (2011) 7.55

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev (2004) 7.51

TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell (2006) 7.49

p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell (2008) 6.88

ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem (2009) 6.34

Myocardial substrate metabolism in the normal and failing heart. Physiol Rev (2005) 6.06

GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell (2003) 5.21

p53 and metabolism. Nat Rev Cancer (2009) 5.05

A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J (2012) 5.03

Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol (2009) 4.95

Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab (2008) 4.91

Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem (2006) 4.57

Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling. Genes Dev (2008) 4.52

IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell (2007) 4.48

Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ (2006) 4.29

Akt1 is required for physiological cardiac growth. Circulation (2006) 4.25

GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell (2007) 4.22

The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond. Trends Cell Biol (2010) 4.15

Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab (2010) 4.08

Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy (2010) 3.99

Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol (2003) 3.97

ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol (2013) 3.88

The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem (2003) 3.83

mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature (2010) 3.81

Identification of a conserved motif required for mTOR signaling. Curr Biol (2002) 3.78

Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell (2012) 3.77

Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell (2004) 3.62

PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science (2013) 3.60

Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci U S A (2005) 3.55

The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res (2007) 3.55

Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell (2012) 3.38

Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science (2012) 3.24

Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene (2006) 3.17

Cell death in the pathogenesis of heart disease: mechanisms and significance. Annu Rev Physiol (2010) 3.16

Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci U S A (2011) 3.14

Regulation of mTOR and cell growth in response to energy stress by REDD1. Mol Cell Biol (2005) 3.14

PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem (2007) 3.09

Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes. Circ Res (2002) 3.08

ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A (2010) 3.03

Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem (2004) 3.00

Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem (2010) 2.93

Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev Cell (2015) 2.84

Glutaminolysis activates Rag-mTORC1 signaling. Mol Cell (2012) 2.82

p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformation. Nat Cell Biol (2008) 2.81

Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science (2015) 2.80

The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. J Biol Chem (2007) 2.77

mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol (2013) 2.73

Stimulation of autophagy by the p53 target gene Sestrin2. Cell Cycle (2009) 2.72

Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem (2005) 2.70

Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J (1998) 2.65

The stress-inducted proteins RTP801 and RTP801L are negative regulators of the mammalian target of rapamycin pathway. J Biol Chem (2005) 2.63

Mitochondrial hexokinase. Release, rebinding, and location. J Biol Chem (1967) 2.58

Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen. J Bioenerg Biomembr (2007) 2.47

Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature (1977) 2.45

Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature (2012) 2.28

Novel role of the small GTPase Rheb: its implication in endocytic pathway independent of the activation of mammalian target of rapamycin. J Biochem (2005) 2.28

Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. Proc Natl Acad Sci U S A (2012) 2.14

Metabolism. Differential regulation of mTORC1 by leucine and glutamine. Science (2015) 2.14

Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ (2007) 2.10

Differential roles of GSK-3β during myocardial ischemia and ischemia/reperfusion. Circ Res (2011) 2.10

Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy. Circulation (2014) 2.07

Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci U S A (2011) 2.06

Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner. Proc Natl Acad Sci U S A (2008) 2.02

Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ (2001) 2.01

SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature (2015) 2.01

Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells. J Biol Chem (2006) 1.98

Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem (2012) 1.98

New nuclear functions of the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase, in mammalian cells. J Cell Biochem (2005) 1.97

Impaired autophagosome clearance contributes to cardiomyocyte death in ischemia/reperfusion injury. Circulation (2012) 1.91