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.