THE EFFECTS OF SINGLET OXYGEN PRODUCED BY PHOTODYNAMIC ACTION ON THE MITOCHONDRIAL PERMEABILITY TRANSITION DIFFER IN ACCORDANCE WITH THE LOCALIZATION PROPERTIES OF THE SENSITIZER

We have examined whether the effects of singlet oxygen produced by photodynamic action on the mitochondrial permeability transition (PT) can be modulated by the localization of photosensitizers in irradiated mitochondria. We have previously shown that oxidation due to singlet oxygen 1O2 generated in hematoporphyrin (HP)-loaded mitochondria can prevent opening of the PT pores, likely after degradation of some critical histidines (Salet et al., 1997, J. Biol. Chem. 272, 21938-21943). In the present study, we have used 3,4',5-trimethylpsoralen (TMP) equally as a photosensitizer of isolated rat liver mitochondria. We now report that TMP binds to protein sites which differ from those of HP. In sharp contrast with HP, TMP-driven photodynamic action triggers per se pore opening. Interestingly, this inducing effect is inhibited in a cyclosporin-like manner when TMP-treated mitochondria are irradiated after addition of mersalyl, a specific reagent protecting thiol groups. This fact suggests that 1O2 oxidation of thiol groups oriented toward the hydrophilic phase is responsible for TMP-photoinduced pore opening. Taken together, these findings demonstrate that 1O2 can activate or inactivate a cellular function such as mitochondrial PT depending on the site where it is produced in the mitochondrial membrane.