Calcium-dependent opening of a non-specific pore in the mitochondrial inner membrane is inhibited at pH values below 7. Implications for the protective effect of low pH against chemical and hypoxic cell damage.
1. The rate of opening of the Ca(2+)-induced non-specific, cyclosporin A-inhibited, pore of the mitochondrial inner membrane of rat heart and liver mitochondria at pH 6.0 was less than 10% of that at pH 7.4. 2. The effect could not be explained by inhibition of Ca2+ uptake into the mitochondria, or of the matrix peptidyl-prolyl cis-trans isomerase (PPIase), or of the Ca(2+)-induced conformational change of the adenine nucleotide translocase. 3. It is suggested that the proposed interaction of matrix PPIase with the 'c' conformation of the adenine nucleotide carrier in the presence of Ca2+ [Griffiths & Halestrap (1991) Biochem. J. 274, 611-614] is inhibited by low pH. 4. The relevance of this to the protective effect of low pH on hypoxic and chemical-induced cell damage is discussed.
Halestrap
A P
AP
Department of Biochemistry, School of Medical Sciences, University of Bristol, U.K.
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000591:Amino Acid Isomerases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000648:ultrastructure; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000648:ultrastructure*; D000226:Mitochondrial ADP, ATP Translocases / Q000737:chemistry; D008933:Mitochondrial Swelling / Q000187:drug effects; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats
D002352:Carrier Proteins; D003524:Cyclosporins; D002731:4-Chloromercuribenzenesulfonate; D000226:Mitochondrial ADP, ATP Translocases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D002118:Calcium