mTOR complex 1 signalling regulates the balance between lipid synthesis and oxidation in hypoxia lymphocytes
Autor: | Yuan Yang, Min Yang, Geng Yin, Qi-Bing Xie, Yan Liang, Xiao-Min Cen, Ying Wang |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Programmed cell death Biophysics Apoptosis mTORC1 lymphocyte Mechanistic Target of Rapamycin Complex 1 Biology cell survival Biochemistry 03 medical and health sciences Lipid oxidation Animals Homeostasis Lymphocytes Molecular Biology Research Articles Cells Cultured PI3K/AKT/mTOR pathway mammalian target of rapamycin Gene knockdown cell apoptosis hypoxia Lipid metabolism Cell Biology Lipid Metabolism Cell Hypoxia Cell biology Mice Inbred C57BL Metabolic pathway 030104 developmental biology biological phenomena cell phenomena and immunity Oxidation-Reduction Intracellular Research Article Signal Transduction |
Zdroj: | Bioscience Reports |
ISSN: | 1573-4935 0144-8463 |
DOI: | 10.1042/bsr20160479 |
Popis: | Mammalian cells adapt to different environmental conditions and alter cellular metabolic pathways to meet the energy demand for survival. Thus, the metabolic regulation of cells under special conditions, such as hypoxia, should be precisely regulated. During the metabolic regulation, mammalian target of rapamycin (mTOR) plays a vital role in the sensing of extracellular stimulations and regulating intracellular adaptations. Here, we report that mTOR complex 1 (mTORC1) signalling is a central regulator of lipid homoeostasis in lymphocytes. In hypoxia, mTORC1 activity is reduced and shifts lipid synthesis to lipid oxidation. Moreover, knockdown tuberous sclerosis complex 1 (TSC1) constitutively activates mTORC1 activity and impairs the hypoxia-induced metabolic shift. Therefore, TSC1 knockdown enhances hypoxia-induced cell death. Re-inactivation of mTORC1 activity via rapamycin may resist hypoxia-induced cell death in TSC1 knockdown lymphocytes. Our findings provide a deep insight into mTORC1 in the metabolic balance of lipid synthesis and oxidation, and imply that mTORC1 activity should be precisely regulated for the lipid homoeostasis in lymphocytes. |
Databáze: | OpenAIRE |
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