• Carola Ledderose, Yi Bao, Markus Lidicky, Johannes Zipperle, Linglin Li, Katharina Strasser, Nathan I Shapiro, and Wolfgang G Junger.
• From the Departments of Surgery and.
• J. Biol. Chem. 2014 Sep 12; 289 (37): 25936-45.

AbstractT cells play a central role in host defense. ATP release and autocrine feedback via purinergic receptors has been shown to regulate T cell function. However, the sources of the ATP that drives this process are not known. We found that stimulation of T cells triggers a spike in cellular ATP production that doubles intracellular ATP levels in <30 s and causes prolonged ATP release into the extracellular space. Cell stimulation triggered rapid mitochondrial Ca(2+) uptake, increased oxidative phosphorylation, a drop in mitochondrial membrane potential (Δψm), and the accumulation of active mitochondria at the immune synapse of stimulated T cells. Inhibition of mitochondria with CCCP, KCN, or rotenone blocked intracellular ATP production, ATP release, intracellular Ca(2+) signaling, induction of the early activation marker CD69, and IL-2 transcription in response to cell stimulation. These findings demonstrate that rapid activation of mitochondrial ATP production fuels the purinergic signaling mechanisms that regulate T cells and define their role in host defense.© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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