Studies on the uptake of porphyrin by isolated rat liver mitochondria.
1. The uptake of deuteroporphyrin by isolated rat liver mitochondria proceeds by two different mechanisms, a passive binding, and a mechanism sensitive to CCCP plus valinomycin, with different pH, temperature and time dependencies. 2. The CCCP plus valinomycin-sensitive uptake of deuteroporphyrin parallels the transmembrane potassium gradient ([K+in]/[K+out]). 3. Only that deuteroporphyrin taken up in parallel to the transmembrane potassium gradient is accessible to ferrochelatase. 4. The uptake of deuteroporphyrin at high concentrations is followed by series of damaging effects on the mitochondria: uncoupling, dissipation of the mitochondrial energy potential, increased ion permeability and leakage of endogenous potassium. 5. The detrimental effects of porphyrins at high concentrations on mitochondrial structure might explain the apparently unrelated metabolic aberrations characteristic of certain porphyric diseases.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D003905:Deuteroporphyrins / Q000378:metabolism*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009840:Oligomycins / Q000494:pharmacology; D011166:Porphyrins / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D014634:Valinomycin / Q000494:pharmacology
D003486:Cyanides; D003905:Deuteroporphyrins; D009840:Oligomycins; D011166:Porphyrins; D014634:Valinomycin; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D011188:Potassium