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 extracellular stimulations and regulating intracellular adaptations. Here, we report that mTORC1 signaling is a central regulator of lipid homeostasis in lymphocyte. In hypoxia, mTORC1 activity is reduced, and shifts lipid synthesis to lipid oxidation. Moreover, knockdown 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 of mTORC1 in the metabolic balance of lipid synthesis and oxidation, and imply that mTORC1 activity should be precisely regulated for the lipid homeostasis in lymphocytes.
- mammalian target of rapamycin
- cell apoptosis
- cell survival
- ©2017 The Author(s)
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