Myc and Metabolism

Sci. Signal., 3 January 2012
Vol. 5, Issue 205, p. ec2
DOI: 10.1126/scisignal.2002813
Immunology

Myc and Metabolism

  1. John F. Foley
  1. Science Signaling, AAAS, Washington, DC 20005, USA

To mount an effective immune response, antigen-specific T cells must rapidly expand in numbers upon activation. The energy requirements to support their rapid proliferation result in a metabolic switch in the T cells from fatty acid β-oxidation and pyruvate oxidation to aerobic glycolysis and the metabolism of glutamine. Thus, proliferating T cells adopt a metabolic profile similar to that of tumor cells (see commentary by Rathmell). Wang et al. studied the gene expression changes that accompanied the activation of mouse T cells and performed computational analysis to identify Myc and hypoxia-inducible factor 1α (HIF-1α) as the transcription factors that most likely controlled the genes responsible for changes in metabolism. Experiments with inhibitors and knockout animals showed that Myc, but not HIF-1α, was required for glycolysis and glutaminolysis in activated T cells and for cellular proliferation. Deletion of Myc also inhibited signaling downstream of the kinase mammalian target of rapamycin (mTOR), which regulates aerobic glycolysis. In addition, the activities of polyamine and nucleotide synthetic pathways were decreased in Myc-deficient cells compared with those in wild-type cells, and the addition of polyamines restored proliferation in activated T cells deprived of glutamine. Together, these data suggest that Myc drives the metabolic reprogramming of proliferating T cells. As Rathmell discusses, these findings may lead to the therapeutic manipulation of lymphocyte metabolism to modulate immune responses.

R. Wang, C. P. Dillon, L. Z. Shi, S. Milasta, R. Carter, D. Finkelstein, L. L. McCormick, P. Fitzgerald, H. Chi, J. Munger, D. R. Green, The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35, 871–882 (2011). [PubMed]

J. C. Rathmell, T cell Myc-tabolism. Immunity 35, 845–846 (2011). [PubMed]

Citation:

J. F. Foley, Myc and Metabolism. Sci. Signal. 5, ec2 (2012).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882