Cell
Volume 82, Issue 3, 11 August 1995, Pages 415-424
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Article
Decoding of cytosolic calcium oscillations in the mitochondria

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Abstract

Frequency-modulated oscillations of cytosolic Ca2+ ([Ca2+]c) are believed to be important in signal transduction, but it has been difficult to correlate [Ca2+]c oscillations directly with the activity of Ca2+-regulated targets. We have studied the control of Ca2+-sensitive mitochondrial dehydrogenases (CSMDHs) by monitoring mitochondria) Ca2+ ([Ca2+]m) and the redox state of flavoproteins and pyridine nucleotides simultaneously with [Ca2+]c in single hepatocytes. Oscillations of [Ca2+]c induced by IP3-dependent hormones were efficiently transmitted to the mitochondria as [Ca2+]m oscillations. Each [Ca2+]m spike was sufficient to cause a maximal transient activation of the CSMDHs and [Ca2+]m oscillations at frequencies above 0.5 per minute caused a sustained activation of mitochondrial metabolism. By contrast, sustained [Ca2+]c increases yielded only transient CSMDH activation, and slow or partial [Ca2+]c elevations were ineffective in increasing [Ca2+]m or stimulating CSMDHs. We conclude that the mitochondria are tuned to oscillating [Ca2+]c signals, the frequency of which can control the CSMDHs over the full range of potential activities.

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