| First Author | Ledderose C | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 37 | Pages | 25936-45 |
| PubMed ID | 25070895 | Mgi Jnum | J:236592 |
| Mgi Id | MGI:5806411 | Doi | 10.1074/jbc.M114.575308 |
| Citation | Ledderose C, et al. (2014) Mitochondria are gate-keepers of T cell function by producing the ATP that drives purinergic signaling. J Biol Chem 289(37):25936-45 |
| abstractText | T 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 (Deltapsim), 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. |
