Studies on the efflux of metalloporphyrin from rat-liver mitochondria. Effect of albumin, globin, haemin and haemoglobin

Abstract

The mechanism by which metalloporphyrins escape from mitochondria was studied in isolated rat-liver mitochondria using Co-deuteroporphyrin as the model compound. During the first 10-15 min of incubation the efflux is about 10% of the total amount of Co-deuteroporphyrin synthesized. The efflux then increases to a 2nd steady-state level of 25-35% after 30-45 min of incubation. The efflux is inversely correlated to the energy state of the mitochondria. Globin at concentrations > 0.4 .mu.mol/l enhances the efflux of Co-deuteroporphyrin, but has no effect on the degree of energy coupling or on the rate of Co-deuteroporphyrin synthesis. The effect of globin can be competitively inhibited by adding hemin. Hemin (0.5-1.0 .mu.mol/l) when added to the medium in the absence of globin reduces the efflux of Co-deuteroporphyrin by 20-30%, but has no effect on the metal-chelatase activity. Neither albumin nor Hb increases the efflux of Co-deuteroporphyrin from intact mitochondria. The efflux of metalloporphyrin is regulated in part by the energy state of the mitochondria and in part by the presence of metalloporphyrin-binding ligands and unattached hemin in the incubation medium.