Effect of pyridine homologues on respiratory control and H+/O ratio in mitochondria.

The effect of pyridine homologues on proton leakage, respiratory control, oxidative phosphorylation, and H+/O ratio in mitochondria have been examined. Up to a concentration of 1 mM, hydrophobic pyridine homologues diminish respiratory control in bovine heart mitochondria by increasing the State 4 respiration rate but have relatively minor effects on the State 3 and the 2,4-dinitrophenol-uncoupled respiration rates. Neither the proton gradient generated by electron transport in mitochondria in the presence of potassium ion and valinomycin, nor the rate of its anaerobic decay was affected by pyridine homologues. These observations suggest that the basal rate of electron transport is governed not directly by proton gradient, but by molecular processes in the energy-transducing membrane which can be affected by the proton gradient. By assuming that pyridine homologues are bound at low concentrations to specific functional groups in the inner membrane, the observed rates of State 4 respiration can be related quantitatively to the concentration of the organic base in solution. The observation that low concentrations of pyridine homologues decrease the H+/O ratio of mitochondria seems difficult to reconcile with the assumption that proton extrusion is driven directly by electron transport.