The effects of singlet oxygen produced by photodynamic action on the mitochondrial permeability transition differ in accordance with the localization of the sensitizer.
We have examined whether the effects of singlet oxygen (1O2) 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 1O2 photogenerated 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). Equally, in the present study we have irradiated mitochondria in the presence of a structurally different photosensitizer producing 1O2, namely 4,5',8-trimethylpsoralen (TMP). Fluorescence studies show 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 when TMP-treated mitochondria are irradiated after addition of mersalyl, a specific reagent protecting thiol groups of the inner mitochondrial membrane that are oriented toward the external hydrophilic phase. This fact suggests that 1O2-mediated thiol oxidation is responsible for TMP-photoinduced pore opening. Taken together, these findings suggest 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.
Moreno
G
G
Laboratoires de Biophysique et de Photobiologie, INSERM U 201 et CNRS UMR 8646, Paris, France. moreno@mnhn.fr
Poussin
K
K
Ricchelli
F
F
Salet
C
C
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects / Q000528:radiation effects; D005454:Fluorescence Polarization; D006415:Hematoporphyrins / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D007473:Ion Channels; D007700:Kinetics; D008027:Light; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D008565:Membrane Proteins / Q000378:metabolism*; D008634:Mersalyl / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism*; D017319:Photosensitizing Agents / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D012542:Scattering, Radiation; D026082:Singlet Oxygen; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013696:Temperature; D014307:Trioxsalen / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D006415:Hematoporphyrins; D007473:Ion Channels; D008081:Liposomes; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017319:Photosensitizing Agents; D013438:Sulfhydryl Compounds; D014475:Uncoupling Agents; D026082:Singlet Oxygen; D015060:1,2-Dipalmitoylphosphatidylcholine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D008634:Mersalyl; D010100:Oxygen; D002118:Calcium; D014307:Trioxsalen