SACCHAROMYCES-CEREVISIAE MUTANTS DEFECTIVE IN HEME-BIOSYNTHESIS AS A TOOL FOR STUDYING THE MECHANISM OF PHOTOTOXICITY OF PORPHYRINS

Mutants of Saccharomyces cerevisiae accumulating uroporphyrin (UP) or protoporphyrin (PP) were used as a model for the in vivo phototoxic ef fect of porphyrins observed in the human skin photosensitivity associa ted with porphyrias (porphyria cutanea tarda and erythropoietic protop orphyria). We have found that UP is localized in vacuoles and PP is pr esent in all compartments except vacuoles in yeast cells. Endogenous P P is much more effective as a photosensitizer of yeast cells than UP. Protoporphyrin action is strictly dependent on the presence of oxygen. In contrast, UP displays a phototoxic effect even if oxygen is not pr esent in the suspension, implicating a free radical mechanism that ope rates in anaerobiosis upon photosensitization by UP, Catalase or super oxide dismutase deficiency affects photosensitization by UP, A possibl e mechanism of UP photosensitizing activity is discussed.