@article{2894,
  keywords = {Animals, Mice, Inbred C57BL, Energy Metabolism, Proteomics, Proteome, Cell Survival, Mitochondria, Metabolic Networks and Pathways, Carbon, Organelle Biogenesis, T-Lymphocytes, Epitopes, CD4-Positive T-Lymphocytes, Lymphocyte Activation, Pyrimidines},
  author = {Noga Ron-Harel and Daniel Santos and Jonathan Ghergurovich and Peter Sage and Anita Reddy and Scott Lovitch and Noah Dephoure and F Kyle Satterstrom and Michal Sheffer and Jessica Spinelli and Steven Gygi and Joshua Rabinowitz and Arlene Sharpe and Marcia Haigis},
  title = {Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon Metabolism for T Cell Activation.},
  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> },
  year = {2016},
  journal = {Cell Metab},
  volume = {24},
  pages = {104-17},
  month = {2016 Jul 12},
  issn = {1932-7420},
  doi = {10.1016/j.cmet.2016.06.007},
  language = {eng},
}