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Recent evidence has shown that SOCE depends critically on mitochondrial sinking of entering Ca<jats:sup>2+<\/jats:sup> to avoid Ca<jats:sup>2+<\/jats:sup>\u2010dependent inactivation. Thus, a role of mitochondria in control of cell proliferation could be anticipated. We show here that activation of SOCE induces cytosolic high [Ca<jats:sup>2+<\/jats:sup>] domains that are large enough to be sensed and avidly taken up by a pool of nearby mitochondria. Prevention of mitochondrial clearance of the entering Ca<jats:sup>2+<\/jats:sup> inhibited both SOCE and cell proliferation in several cell types including Jurkat and human colon cancer cells. In addition, we find that therapeutic concentrations of salicylate, the major metabolite of aspirin, depolarize partially mitochondria and inhibit mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake, as revealed by mitochondrial Ca<jats:sup>2+<\/jats:sup> measurements with targeted aequorins. This salicylate\u2010induced inhibition of mitochondrial Ca<jats:sup>2+<\/jats:sup> sinking prevented SOCE and impaired cell growth of Jurkat and human colon cancer cells. Finally, direct blockade of SOCE by the pyrazole derivative BTP\u20102 was sufficient to arrest cell growth. Taken together, our results reveal that cell proliferation depends critically on mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake and suggest that inhibition of tumour cell proliferation by salicylate may be due to interference with mitochondrial Ca<jats:sup>2+<\/jats:sup> uptake, which is essential for sustaining SOCE. This novel mechanism may contribute to explaining the reported anti\u2010proliferative and anti\u2010tumoral actions of aspirin and dietary salicylates.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.100586","type":"journal-article","created":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T01:19:20Z","timestamp":1134091160000},"page":"57-73","source":"Crossref","is-referenced-by-count":72,"title":["Cell proliferation depends on mitochondrial Ca<sup>2+<\/sup> uptake: inhibition by salicylate"],"prefix":"10.1113","volume":"571","author":[{"given":"Luc\u00eda","family":"N\u00fa\u00f1ez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth 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