Periodate-oxidized ATP stimulates the permeability transition of rat liver mitochondria.
Periodate-oxidized ADP (oADP)2 and periodate-oxidized ATP (oATP) stimulate the permeability transition in energized rat liver mitochondria measured as the Ca2+-efflux induced by Ca2+ and Pi. In the presence of Mg2+ and Pi, mitochondria lose intramitochondrial adenine nucleotides at a slow rate. oATP induces a strong decrease of the matrix adenine nucleotides which is inhibited by carboxyatractyloside. Under these conditions, Mg2+ prevents the opening of the permeability transition pore. EGTA prevents the Pi-induced slow efflux of adenine nucleotides, but is without effect on the oATP-induced strong decrease of adenine nucleotides. This oATP-induced strong adenine nucleotide efflux is inhibited by ADP. oATP reduces the increase of matrix adenine nucleotides occurring when the mitochondria are incubated with Mg2+ and ATP. This effect of oATP is also prevented by carboxyatractyloside. oATP is not taken up by the mitochondria. It is suggested that oATP induces a strong efflux of matrix adenine nucleotides by the interaction with the ADP/ATP carrier from the cytosolic side. The induction of the mitochondrial permeability transition by oADP and oATP is attributed to two mechanisms-a strong decrease in the intramitochondrial adenine nucleotide content, especially that of ADP, and a stabilization of the c-conformation of the ADP/ATP carrier.
Henke
W
W
Research Division, Department of Urology, University Hospital Charité, Humboldt University, Schumannstrasse 20/21, D-10098 Berlin, Germany. henke@rz.charite.hu-berlin.de
Hagen
T
T
Jung
K
K
Loening
S A
SA
D000227:Adenine Nucleotides / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects*; D010084:Oxidation-Reduction; D010504:Periodic Acid; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
D000227:Adenine Nucleotides; D010504:Periodic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C009288:metaperiodate; D002118:Calcium