Decrease in mitochondrial energy couplings by thyroid hormones: a physiological effect rather than a pathological hyperthyroidism consequence

The effect of the in vivo thyroid status on mitochondrial membrane potential (Delta Psi(m)) in isolated rat hepatocytes was studies by means of a cytofluorimetric technique and the Delta Psi(m)-specific probe JC-1. It is shown that the Delta Psi(m) level decreases in the order hypothyroid > euthyroid > hyperthyroid, Polarographic measurement of the hepatocyte respiratory rates revealed an opposite trend of values: the highest respiratory rate in hepatocytes from hyperthyroid animals, the lowest in those from hypothyroid ones. This means that mitochondrial energy coupling is highest in hypothyroid hepatocytes and lowest in hyperthyroid hepatocytes. 6-Ketocholestanol added to hepatocytes failed to counterbalance the uncoupling effect of thyroid hormones on Delta Psi(m) and respiration rate. Under the same conditions, 6-ketocholestanol appeared to be effective in recoupling of respiration uncoupled by low concentrations of the artificial protonophore FCCP, The mechanism and possible physiological functions of the thyroid hormone-induced decrease in mitochondrial energy coupling are discussed. (C) 1998 Federation of European Biochemical Societies.