|Title||Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Ron-Harel, N, Santos, D, Ghergurovich, JM, Sage, PT, Reddy, A, Lovitch, SB, Dephoure, N, F Satterstrom, K, Sheffer, M, Spinelli, JB, Gygi, S, Rabinowitz, JD, Sharpe, AH, Haigis, MC|
|Date Published||2016 Jul 12|
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.
|Alternate Journal||Cell Metab.|
|Grant List||R01 DK103295 / DK / NIDDK NIH HHS / United States|