AMPK and mTOR in cellular energy homeostasis and drug targets.
The mammalian target of rapamycin (mTOR) is a central controller of cell growth and proliferation. mTOR forms two distinct complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 is regulated by multiple signals such as growth factors, amino acids, and cellular energy and regulates numerous essential cellular processes including translation, transcription, and autophagy. The AMP-activated protein kinase (AMPK) is a cellular energy sensor and signal transducer that is regulated by a wide array of metabolic stresses. These two pathways serve as a signaling nexus for regulating cellular metabolism, energy homeostasis, and cell growth, and dysregulation of each pathway may contribute to the development of metabolic disorders such as obesity, type 2 diabetes, and cancer. This review focuses on our current understanding of the relationship between AMPK and mTORC1 signaling and discusses their roles in cellular and organismal energy homeostasis.
Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Ken
K
Inoki
Joungmok
J
Kim
Kun-Liang
KL
Guan
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D001343:Autophagy / Q000502:physiology; D049109:Cell Proliferation; D016503:Drug Delivery Systems / Q000379:methods*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D014176:Protein Biosynthesis / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000596:Amino Acids; C493245:CRTC2 protein, human; D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases