Inhibition of oxidative phosphorylation by organotin thiocarbamates.
A series of triphenyl-, tricyclohexyl- and tribenzyltin compounds have been synthesized and examined as inhibitors of mitochondrial oxidative phosphorylation. All compounds tested inhibit oxidative phosphorylation linked to succinate oxidation by potato tuber mitochondria. All of the organotin compounds inhibit ADP-stimulated O2 uptake linked to succinate oxidation with concentrations for 50% inhibition in the range 2-50 microM. This inhibition is not due to inhibition of electron transport from succinate to O2 per se: none of the organotin compounds at 50 microM substantially inhibit the rate of succinate oxidation in the presence of 2,4-dinitrophenol. Representative organotin compounds at 0.5-50 microM do not act as uncouplers of succinate oxidation. It is concluded that the organotin compounds act as energy transfer inhibitors to inhibit oxidative phosphorylation in potato tuber mitochondria. A similar mode of action of representative organotin compounds was found with rat liver mitochondria. These organotin compounds inhibit a hydrophobic Ca2+-dependent plant protein kinase in the absence but not in the presence of thiols.
Department of Chemistry, La Trobe University, Bundoora, Victoria, Australia.
S
S
Chandra
G M
GM
Polya
B D
BD
James
R J
RJ
Magee
D000818:Animals; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009947:Organotin Compounds / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000494:pharmacology*
D009947:Organotin Compounds; D013859:Thiocarbamates; D011494:Protein Kinases