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Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13807-12.

Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming.

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1
Department of Biomedical Sciences, Consiglio Nazionale delle Ricerche Center for Study of Biomembranes, University of Padova, 35131 Padova, Italy.

Abstract

In recent years, mitochondria have emerged as important targets of agonist-dependent increases in cytosolic Ca(2+) concentration. Here, we analyzed the significance of Ca(2+) signals for the modulation of organelle function by directly measuring mitochondrial and cytosolic ATP levels ([ATP](m) and [ATP](c), respectively) with specifically targeted chimeras of the ATP-dependent photoprotein luciferase. In both HeLa cells and primary cultures of skeletal myotubes, stimulation with agonists evoking cytosolic and mitochondrial Ca(2+) signals caused increases in [ATP](m) and [ATP](c) that depended on two parameters: (i) the amplitude of the Ca(2+) rise in the mitochondrial matrix, and (ii) the availability of mitochondrial substrates. Moreover, the Ca(2+) elevation induced a long-lasting priming that persisted long after agonist washout and caused a major increase in [ATP](m) upon addition of oxidative substrates. These results demonstrate a direct role of mitochondrial Ca(2+) in driving ATP production and unravel a form of cellular memory that allows a prolonged metabolic activation in stimulated cells.

PMID:
10570154
PMCID:
PMC24146
[Indexed for MEDLINE]
Free PMC Article
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