Decoding of cytosolic calcium oscillations in the mitochondria

Frequency-modulated oscillations of cytosolic Ca 2+ ([Ca 2+] c) are believed to be important in signal transduction, but it has been difficult to correlate [Ca 2+] c oscillations directly with the activity of Ca 2+-regulated targets. We have studied the control of Ca 2+-sensitive mitochondrial dehyd...

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Bibliographic Details
Published in:Cell 1995-08, Vol.82 (3), p.415-424
Main Authors: Hajnóczky, György, Robb-Gaspers, Lawrence D, Seitz, Michele B, Thomas, Andrew P
Format: Article
Language:English
Subjects:
Animals
Calcium - physiology
Liver - physiology
Male
Mitochondria, Liver - physiology
Oxidation-Reduction
Oxidoreductases - physiology
Rats
Rats, Sprague-Dawley
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Summary:Frequency-modulated oscillations of cytosolic Ca 2+ ([Ca 2+] c) are believed to be important in signal transduction, but it has been difficult to correlate [Ca 2+] c oscillations directly with the activity of Ca 2+-regulated targets. We have studied the control of Ca 2+-sensitive mitochondrial dehydrogenases (CSMDHs) by monitoring mitochondria) Ca 2+ ([Ca 2+] m) and the redox state of flavoproteins and pyridine nucleotides simultaneously with [Ca 2+] c in single hepatocytes. Oscillations of [Ca 2+] c induced by IP 3-dependent hormones were efficiently transmitted to the mitochondria as [Ca 2+] m oscillations. Each [Ca 2+] m spike was sufficient to cause a maximal transient activation of the CSMDHs and [Ca 2+] m oscillations at frequencies above 0.5 per minute caused a sustained activation of mitochondrial metabolism. By contrast, sustained [Ca 2+] c increases yielded only transient CSMDH activation, and slow or partial [Ca 2+] c elevations were ineffective in increasing [Ca 2+] m or stimulating CSMDHs. We conclude that the mitochondria are tuned to oscillating [Ca 2+] c signals, the frequency of which can control the CSMDHs over the full range of potential activities.
ISSN:0092-8674
1097-4172
DOI:10.1016/0092-8674(95)90430-1