线粒体生物发生
细胞生物学
线粒体
生物
细胞生长
生物发生
蛋白质组
细胞代谢
细胞
新陈代谢
生物化学
基因
作者
Noga Ron-Harel,Daniel Ditzel Santos,Jonathan M. Ghergurovich,Peter T. Sage,Anita Reddy,Scott B. Lovitch,Noah Dephoure,F. Kyle Satterstrom,Michal Sheffer,Jessica B. Spinelli,Steven P. Gygi,Joshua D. Rabinowitz,Arlene H. Sharpe,Marcia C. Haigis
标识
DOI:10.1016/j.cmet.2016.06.007
摘要
Naive T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naive CD4(+) T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one-carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one-carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one-carbon metabolism that is critical for T cell activation and survival.
科研通智能强力驱动
Strongly Powered by AbleSci AI