Comparative study on uncoupling effects of laurate and lauryl sulfate on rat liver and skeletal muscle mitochondria

Uncoupling effects of laurate and lauryl sulfate have been studied in the i solated rat liver and skeletal muscle mitochondria. In the oligomycin-treat ed liver mitochondria, 0.02 mM laurate or 0.16 mM lauryl sulfate caused a t wo-fold stimulation of respiration, accompanied by a membrane potential dec rease. Carboxyatractylate (CAtr) and glutamate (or aspartate) strongly decr ease the effect of laurate and lauryl sulfate on respiratory rate and membr ane potential (the recoupling effect). With both uncouplers, this effect is maximal for CAtr and glutamate (aspartate) at pH 7.8 and 7.0, respectively . Tetraphenyl phosphonium cations, which decrease negative membrane charges , cause an alkaline shift of these pH dependences. Small amounts of lauryl sulfate, which increase the membrane negative charge, induce the opposite s hift when laurate is used as an uncoupler. ADP, but not GDP, partially reco uple with both laurate and lauryl sulfate. We conclude that lauryl sulfate- induced uncoupling in rat liver, like the uncoupling induced by laurate, is mediated by the ATP/ADP and glutamate/aspartate antiporters. In skeletal m uscle mitochondria uncoupled by laurate, 200 mu M GDP causes partial recoup ling which can be enhanced by a subsequent additions of CAtr, glutamate and serum albumin. CAtr added before GDP promotes a larger recoupling than whe n added after GDP and prevents the subsequent effect of GDP. ADP is effecti ve as recoupler at lower concentrations that GDP, whereas CDP is without in fluence. Lauryl sulfate uncoupling of skeletal muscle mitochondria is GDP-r esistant but is sensitive to ADP, CAtr, glutamate and serum albumin. Our da ta suggest that in skeletal muscle mitochondria a GDP-sensitive mechanism i s involved in uncoupling induced by laurate. This mechanism is absent in li ver mitochondria. Possible mechanisms of laurate and lauryl sulfate-induced uncoupling are discussed, (C) 2000 Elsevier Science B.V. All rights reserv ed.