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

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

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)104-117
Number of pages14
JournalCell Metabolism
Volume24
Issue number1
DOIs
StatePublished - Jul 12 2016

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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