Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation

作者：Ron Harel Noga; Santos Daniel; Ghergurovich Jonathan M; Sage Peter T; Reddy Anita; Lovitch Scott B; Dephoure Noah; Satterstrom F Kyle; Sheffer Michal; Spinelli Jessica B; Gygi Steven; Rabinowitz Joshua D; Sharpe Arlene H; Haigis Marcia C

来源：Cell Metabolism, 2016, 24(1): 104-117.

DOI：10.1016/j.cmet.2016.06.007

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.

• 出版日期2016-7-12