mTOR couples cellular nutrient sensing to organismal metabolic homeostasis

被引:286
作者
Howell, Jessica J. [1 ]
Manning, Brendan D. [1 ]
机构
[1] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
DIET-INDUCED OBESITY; TUBEROUS SCLEROSIS COMPLEX-2; HEPATIC INSULIN-RESISTANCE; P70; S6; KINASE; MAMMALIAN TARGET; ADIPOCYTE DIFFERENTIATION; SKELETAL-MUSCLE; BODY-WEIGHT; FOOD-INTAKE; BETA-CELLS;
D O I
10.1016/j.tem.2010.12.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The mammalian target of rapamycin complex 1 (mTORC1) has the ability to sense a variety of essential nutrients and respond by altering cellular metabolic processes. Hence, this protein kinase complex is poised to influence adaptive changes to nutrient fluctuations toward the maintenance of whole-body metabolic homeostasis. Defects in mTORC1 regulation, arising from either physiological or genetic conditions, are believed to contribute to the metabolic dysfunction underlying a variety of human diseases, including type 2 diabetes. We are just now beginning to gain insights into the complex tissue-specific functions of mTORC1. In this review, we detail the current knowledge of the physiological functions of mTORC1 in controlling systemic metabolism, with a focus on advances obtained through genetic mouse models.
引用
收藏
页码:94 / 102
页数:9
相关论文
共 103 条
[71]   Adipose-Specific Knockout of raptor Results in Lean Mice with Enhanced Mitochondrial Respiration [J].
Polak, Pazit ;
Cybulski, Nadine ;
Feige, Jerome N. ;
Auwerx, Johan ;
Rueegg, Markus A. ;
Hall, Michael N. .
CELL METABOLISM, 2008, 8 (05) :399-410
[72]   SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth [J].
Porstmann, Thomas ;
Santos, Claudio R. ;
Griffiths, Beatrice ;
Cully, Megan ;
Wu, Mary ;
Leevers, Sally ;
Griffiths, John R. ;
Chung, Yuen-Li ;
Schulze, Almut .
CELL METABOLISM, 2008, 8 (03) :224-236
[73]   Disruption of Tsc2 in pancreatic β cells induces β cell mass expansion and improved glucose tolerance in a TORC1-dependent manner [J].
Rachdi, Latif ;
Balcazar, Norman ;
Osorio-Duque, Fernando ;
Elghazi, Lynda ;
Weiss, Aaron ;
Gould, Aaron ;
Chang-Chen, Karen J. ;
Gambello, Michael J. ;
Bernal-Mizrachi, Ernesto .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (27) :9250-9255
[74]   Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling [J].
Radimerski, T ;
Montagne, J ;
Hemmings-Mieszczak, M ;
Thomas, G .
GENES & DEVELOPMENT, 2002, 16 (20) :2627-2632
[75]   Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development [J].
Rennebeck, G ;
Kleymenova, EV ;
Anderson, R ;
Yeung, RS ;
Artzt, K ;
Walker, CL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15629-15634
[76]   Making synaptic plasticity and memory last: mechanisms of translational regulation [J].
Richter, Joel D. ;
Klann, Eric .
GENES & DEVELOPMENT, 2009, 23 (01) :1-11
[77]   Muscle inactivation of mTOR causes metabolic and dystrophin defects leading to severe myopathy [J].
Risson, Valerie ;
Mazelin, Laetitia ;
Roceri, Mila ;
Sanchez, Herve ;
Moncollin, Vincent ;
Corneloup, Claudine ;
Richard-Bulteau, Helene ;
Vignaud, Alban ;
Baas, Dominique ;
Defour, Aurelia ;
Freyssenet, Damien ;
Tanti, Jean-Francois ;
Le-Marchand-Brustel, Yannick ;
Ferrier, Bernard ;
Conjard-Duplany, Agnes ;
Romanino, Klaas ;
Bauche, Stephanie ;
Hantai, Daniel ;
Mueller, Matthias ;
Kozma, Sara C. ;
Thomas, George ;
Rueegg, Markus A. ;
Ferry, Arnaud ;
Pende, Mario ;
Bigard, Xavier ;
Koulmann, Nathalie ;
Schaeffer, Laurent ;
Gangloff, Yann-Gael .
JOURNAL OF CELL BIOLOGY, 2009, 187 (06) :859-874
[78]   Effect of mTOR inhibitor on body weight:: from an experimental rat model to human transplant patients [J].
Rovira, Jordi ;
Arellano, Edgar Marcelo ;
Burke, James T. ;
Brault, Yves ;
Moya-Rull, Daniel ;
Banon-Maneus, Elisenda ;
Ramirez-Bajo, Maria J. ;
Gutierrez-Dalmau, Alex ;
Revuelta, Ignacio ;
Quintana, Luis F. ;
Campistol, Josep M. ;
Diekmann, Fritz .
TRANSPLANT INTERNATIONAL, 2008, 21 (10) :992-998
[79]   Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis [J].
Ruvinsky, I ;
Sharon, N ;
Lerer, T ;
Cohen, H ;
Stolovich-Rain, M ;
Nir, T ;
Dor, Y ;
Zisman, P ;
Meyuhas, O .
GENES & DEVELOPMENT, 2005, 19 (18) :2199-2211
[80]   The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 [J].
Sancak, Yasemin ;
Peterson, Timothy R. ;
Shaul, Yoav D. ;
Lindquist, Robert A. ;
Thoreen, Carson C. ;
Bar-Peled, Liron ;
Sabatini, David M. .
SCIENCE, 2008, 320 (5882) :1496-1501