The decrease of mitochondrial substrate uptake caused by trialkyltin and trialkyl-lead compounds in chloride media and its relevance to inhibition of oxidative phosphorylation.
1. In a 100 mM-KCl medium (pH 6.8) containing ATP, triethyltin (1 muM) causes a decrease in the uptake of pyruvate, malate, citrate or beta-hydroxybutyrate by rat liver mitochondria, but no decrease is observed in a 100 mM-KNO3 medium. This response is not modified by the presence of rotenone in the incubation medium. 2. In the KCl medium at least 1 muM-triethyltin is required to cause maximum inhibition of pyruvate uptake. 3. Trimethyltin, tributyltin and the trialkyl-lead analogues at 1 muM, to varying degrees, also cause a decrease in pyruvate uptake by mitochondria only in the KCl medium. 4. Triethyltin stimulates resting respiration of mitochondria with all the substrates tested in the KCl medium but not in the KNO3 medium, yet this stimulation of O2 uptake occurs under conditions when substrate uptake is decreased. 5. In contrast, both O2 uptake during state 3 respiration and ATP synthesis when linked to the oxidation of pyruvate, malate or citrate are strongly inhibited by 1 muM-triethyltin in a KCl medium, but O2 uptake and ATP synthesis during the oxidation of beta-hydroxybutyrate are only slightly affected. In a KNO3 medium O2 uptake and ATP synthesis linked to the oxidation of all substrates are only slightly affected. 6. The relevance of the decrease in substrate uptake by mitochondria caused by triethyltin in a KCl medium to the greater sensitivity of various mitochondrial functions observed in vitro is discussed. It is concluded that decrease of matrix substrate content is probably not the major cause of the greater sensitivity of oxidative phosphorylation to triethyltin in a KCl medium observed previously.
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002951:Citrates / Q000378:metabolism; D000882:Haplorhini; D066298:In Vitro Techniques; D007854:Lead / Q000031:analogs & derivatives* / Q000494:pharmacology; D008293:Malates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption; D011189:Potassium Chloride / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D012402:Rotenone; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D002951:Citrates; D008293:Malates; D009566:Nitrates; D011773:Pyruvates; D014220:Trialkyltin Compounds; D012402:Rotenone; D007854:Lead; D011189:Potassium Chloride; D000255:Adenosine Triphosphate