title: mTOR complex 1 signalling regulates the balance between lipid synthesis and oxidation in hypoxia lymphocytes.
abstract: 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.
authors.affiliation: Department of General Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Cen
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu 610041, China qibingxie@126.com.
authors.forename: Qi-Bing
authors.initials: QB
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006706:Homeostasis; D050356:Lipid Metabolism; D008214:Lymphocytes / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D000076222:Mechanistic Target of Rapamycin Complex 1
keywords: cell apoptosis; cell survival; hypoxia; lymphocyte; mammalian target of rapamycin