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Sci. STKE, 26 June 2007
Vol. 2007, Issue 392, p. tw223
[DOI: 10.1126/stke.3922007tw223]

EDITORS' CHOICE

Metabolism Channeling a Metabolic Message

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

In many cells, loss of calcium from intracellular stores leads to calcium influx through store-operated calcium release-activated calcium (CRAC) channels; the development of microdomains of increased calcium concentration at the mouths of open CRAC channels elicits their rapid inactivation. Incoming calcium is accumulated in mitochondria, where it stimulates mitochondrial respiration and the production of ATP, thereby limiting calcium-dependent CRAC channel inactivation and sustaining calcium entry. Bakowski and Parekh recorded whole-cell CRAC currents of RBL-1 (rat basophilic leukemia) cells and found that pyruvic acid, a rate-limiting substrate for mitochondrial respiration, decreased rapid inactivation of CRAC channels. Pyruvate-derived metabolites had little or no effect on CRAC channel inactivation, nor did the effects of pyruvate depend on calcium uptake into mitochondria, or mitochondrial production of ATP. Experiments in which sodium replaced calcium as the ion carrying charge through the channel suggested that pyruvate interfered with the ability of calcium to mediate rapid inactivation of the CRAC channel. Thus, the authors propose that fluctuations in cytoplasmic pyruvate concentration--which would occur as a result of changes in mitochondrial respiration--provide a mechanism that directly links energy metabolism to the regulation of calcium influx.

D. Bakowski, A. B. Parekh, Regulation of store-operated calcium channels by the intermediary metabolite pyruvic acid. Curr. Biol. 17, 1076-1081 (2007). [PubMed]

Citation: E. M. Adler, Channeling a Metabolic Message. Sci. STKE 2007, tw223 (2007).



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