Trifluoperazine inhibition of electron transport and adenosine triphosphatase in plant mitochondria.
Trifluoperazine inhibits ADP-stimulated respiration in mung bean (Phaseolus aureus) mitochondria when either NADH, malate, or succinate serve as substrates (IC50 values of 56, 59, and 55 microM, respectively). Succinate:ferricyanide oxidoreductase activity of these mitochondria was inhibited to a similar extent. The oxidation of ascorbate/TMPD was also sensitive to the phenothiazine (IC50 = 65 microM). Oxidation of exogenous NADH was inhibited by trifluoperazine even in the presence of excess EGTA [ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid] (IC50 = 60 microM), indicating an interaction with the electron transport chain rather than with the dehydrogenase itself. In contrast, substrate oxidation in Voodoo lily (Sauromatum guttatum) mitochondria was relatively insensitive to the phenothiazine. The results suggest the bc1 complex to be a major site of inhibition. The membrane potential of energized mung bean mitochondria was depressed by micromolar concentrations of trifluoperazine, suggesting an effect on the proton-pumping capability of these mitochondria. Membrane-bound and soluble ATPases were equally sensitive to trifluoperazine (IC50 of 28 microM for both), implying the site of inhibition to be on the F1. Inhibition of the soluble ATPase was not affected by EGTA, CaCl2, or exogenous calmodulin. Trifluoperazine inhibition of electron transport and phosphorylation in plant mitochondria appears to be due to an interaction with a protein of the organelle that is not calmodulin.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III; D007887:Fabaceae; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010944:Plants / Q000648:ultrastructure*; D010946:Plants, Medicinal; D011808:Quinone Reductases / Q000037:antagonists & inhibitors; D014268:Trifluoperazine / Q000494:pharmacology*; D014675:Vegetables
D009097:Multienzyme Complexes; D014268:Trifluoperazine; D000244:Adenosine Diphosphate; D011808:Quinone Reductases; D000251:Adenosine Triphosphatases; D014450:Electron Transport Complex III