Agaric acid induces mitochondrial permeability transition through its interaction with the adenine nucleotide translocase. Its dependence on membrane fluidity.
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.
García
Noemí
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, DF 014080, Mexico.
Zazueta
Cecilia
C
Pavón
Natalia
N
Chávez
Edmundo
E
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019343:Citric Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004801:Eosine Yellowish-(YS) / Q000031:analogs & derivatives / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D007653:Ketocholesterols / Q000494:pharmacology; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D000226:Mitochondrial ADP, ATP Translocases / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D013439:Sulfhydryl Reagents / Q000378:metabolism; D013696:Temperature
D007653:Ketocholesterols; D013439:Sulfhydryl Reagents; D019343:Citric Acid; C063833:6-ketocholestanol; C011396:agaric acid; D000244:Adenosine Diphosphate; C033531:eosin maleimide; D000226:Mitochondrial ADP, ATP Translocases; D002118:Calcium; D004801:Eosine Yellowish-(YS)