Abstract
The effect of agaric acid as inducer of mitochondrial permeability transition was studied. It was found that: (i) agaric acid (AA) promoted efflux of accumulated Ca2+, collapse of transmembrane potential, and mitochondrial swelling; (ii) these effects depend on membrane fluidity; (iii) ADP inhibited the effect of AA on Ca2+ efflux, and (iv) AA blocked binding of the sulfhydryl reagent, eosin-5-maleimide, to the adenine nucleotide translocase. It is proposed that AA induces pore opening through binding of the citrate moiety to the ADP/ATP carrier; this interaction must be stabilized by insertion of the alkyl chain in the lipid milieu of the membrane.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Diphosphate / pharmacology
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Animals
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Calcium / metabolism
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Citric Acid / analogs & derivatives*
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Citric Acid / antagonists & inhibitors
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Citric Acid / pharmacology
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Eosine Yellowish-(YS) / analogs & derivatives
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Eosine Yellowish-(YS) / metabolism
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Intracellular Membranes / drug effects
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Intracellular Membranes / physiology*
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Ketocholesterols / pharmacology
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Membrane Fluidity / drug effects
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Membrane Fluidity / physiology*
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Membrane Potentials / drug effects
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Mitochondria / drug effects
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Mitochondria / physiology*
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Mitochondria / ultrastructure
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Mitochondrial ADP, ATP Translocases / drug effects*
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Mitochondrial ADP, ATP Translocases / metabolism
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Mitochondrial Swelling / drug effects
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Rats
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Sulfhydryl Reagents / metabolism
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Temperature
Substances
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Ketocholesterols
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Sulfhydryl Reagents
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Citric Acid
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6-ketocholestanol
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agaric acid
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Adenosine Diphosphate
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eosin maleimide
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Mitochondrial ADP, ATP Translocases
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Calcium
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Eosine Yellowish-(YS)