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

TitleMitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation.
Publication TypeJournal Article
Year of Publication2016
AuthorsRon-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
JournalCell Metab
Volume24
Issue1
Pagination104-17
Date Published2016 07 12
ISSN1932-7420
KeywordsAnimals, Carbon, CD4-Positive T-Lymphocytes, Cell Survival, Energy Metabolism, Epitopes, Lymphocyte Activation, Metabolic Networks and Pathways, Mice, Inbred C57BL, Mitochondria, Organelle Biogenesis, Proteome, Proteomics, Pyrimidines, T-Lymphocytes
Abstract

<p>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.</p>

DOI10.1016/j.cmet.2016.06.007
Alternate JournalCell Metab.
PubMed ID27411012
PubMed Central IDPMC5330619
Grant ListHHSN272201100018C / AI / NIAID NIH HHS / United States
R01 DK103295 / DK / NIDDK NIH HHS / United States
T32 DK007260 / DK / NIDDK NIH HHS / United States
T32 HG003284 / HG / NHGRI NIH HHS / United States