4.8 Article

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

Journal

CELL METABOLISM
Volume 24, Issue 1, Pages 104-117

Publisher

CELL PRESS
DOI: 10.1016/j.cmet.2016.06.007

Keywords

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Funding

  1. NIH/NIAID [HHSN272201100018C]
  2. F. Hoffmann-La Roche Ltd.
  3. Glenn Foundation for Medical Research
  4. Ludwig center at Harvard
  5. European Molecular Biology Organization
  6. Portuguese Foundation for Science and Technology (FCT-MCTES)

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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.

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