Inhibition of mitochondrial permeability transition by low pH is associated with less extensive membrane protein thiol oxidation.
Ca2+ and inorganic phosphate-induced mitochondrial swelling and membrane protein thiol oxidation, which are associated with mitochondrial permeability transition, are inhibited by progressively decreasing the incubation medium pH between 7.2 and 6.0. Nevertheless, the detection of mitochondrial H2O2 production under these conditions is increased. Permeability transition induced by phenylarsine oxide, which promotes membrane protein thiol cross-linkage in a process independent of Ca2+ or reactive oxygen species, is also strongly inhibited in acidic incubation media. In addition, we observed that the decreased protein thiol reactivity with phenylarsine oxide or phenylarsine oxide-induced swelling at pH 6.0 is reversed by diethyl pyrocarbonate, in a hydroxylamine-sensitive manner. These results provide evidence that the inhibition of mitrochondrial permeability transition observed at lower incubation medium pH is mediated by a decrease in membrane protein thiol reactivity, related to the protonation of protein histidyl residues.
Teixeira
B M
BM
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, SP, Brazil.
Kowaltowski
A J
AJ
Castilho
R F
RF
Vercesi
A E
AE
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D019811:Hydroxylamine / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D001152:Arsenicals; D007476:Ionophores; D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; C029341:oxophenylarsine; D012710:Serum Albumin, Bovine; D019811:Hydroxylamine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000001:Calcimycin; D000968:Antimycin A; D004047:Diethyl Pyrocarbonate; D002118:Calcium