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 pot ential (Delta Psi(m)) in isolated rat hepatocytes was studies by means of a cytofluorimetric technique and the Delta Psi(m)-specific probe J C-1. It is shown that the Delta Psi(m) level decreases in the order hy pothyroid > euthyroid > hyperthyroid, Polarographic measurement of the hepatocyte respiratory rates revealed an opposite trend of values: th e highest respiratory rate in hepatocytes from hyperthyroid animals, t he lowest in those from hypothyroid ones. This means that mitochondria l energy coupling is highest in hypothyroid hepatocytes and lowest in hyperthyroid hepatocytes. 6-Ketocholestanol added to hepatocytes faile d to counterbalance the uncoupling effect of thyroid hormones on Delta Psi(m) and respiration rate. Under the same conditions, 6-ketocholest anol appeared to be effective in recoupling of respiration uncoupled b y low concentrations of the artificial protonophore FCCP, The mechanis m and possible physiological functions of the thyroid hormone-induced decrease in mitochondrial energy coupling are discussed. (C) 1998 Fede ration of European Biochemical Societies.