Abstract
Mitochondria contribute to the maintenance of the intracellular Ca2+ homeostasis by taking up and releasing the cation via separate and specific pathways. The molecular details of the release pathway are elusive but its stimulation by the cross-linking of some vicinal thiols and consequently NAD+ hydrolysis are known. Thiol cross-linking and NAD+ hydrolysis can be achieved by addition of peroxynitrite (ONOO-), the product of the reaction between superoxide (O2-) and nitric oxide (nitrogen monoxide, NO*) to mitochondria. Mitochondria contain an NO synthase (mtNOS), which is stimulated by Ca2+, and are a copious source of O2-. We show here that intramitochondrially formed ONOO- stimulates the specific, NAD+-linked Ca2+ release from mitochondria. Our findings that upon Ca2+ uptake mtNOS is stimulated, that ONOO- is formed, and that Ca2+ is subsequently released from intact mitochondria suggest the existence of a feedback loop, which prevents overloading of mitochondria with Ca2+.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism*
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Feedback
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Female
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Free Radical Scavengers / pharmacology
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Free Radicals / antagonists & inhibitors
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Free Radicals / metabolism
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Homeostasis / drug effects
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Membrane Potentials / drug effects
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Metalloporphyrins / pharmacology
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Mitochondria, Liver / drug effects
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Mitochondria, Liver / enzymology
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Mitochondria, Liver / metabolism*
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NAD / metabolism
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Nitrates / metabolism*
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Nitrates / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism*
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Oxidants / metabolism
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Oxidants / pharmacology
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Oxidation-Reduction / drug effects
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Rats
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Rats, Wistar
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Rotenone / pharmacology
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omega-N-Methylarginine / pharmacology
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tert-Butylhydroperoxide / pharmacology
Substances
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Free Radical Scavengers
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Free Radicals
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Metalloporphyrins
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Nitrates
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Oxidants
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manganese(III)-tetrakis(4-benzoic acid)porphyrin
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Rotenone
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NAD
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peroxynitric acid
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omega-N-Methylarginine
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tert-Butylhydroperoxide
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Nitric Oxide Synthase
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Calcium