Inactivation of mitochondrial electron transport by photosensitization of a pheophorbide a derivative.
We examined the damage to mitochondrial electron transport caused by photosensitization of a pheophorbide a derivative, DH-I-180-3, shown recently to induce necrosis of lung carcinoma cells with low dark toxicity. Confocal microscopy showed that DH-I-180-3 co-localized with dihydrorhodamine-123 suggesting that it mainly accumulates in mitochondria. The photosensitizer alone in the dark did not affect mitochondrial electron transport. Illumination of isolated mitochondria in the presence of DH-I-180-3 resulted in inhibition of both NADH- and succinate-dependent respiration. Measurement of the activity of each component of the electron transport chain revealed that Complex I and III were very susceptible to the treatment whereas Complex IV was resistant. We conclude that the photosensitizer is localized in mitochondria and, upon illumination, produces reactive oxygen species that inactivate Complexes I and III.
Kim
Chang Su
CS
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Lee
Chang-Hee
CH
Lee
Phil Ho
PH
Han
Sanghwa
S
D000818:Animals; D016227:Benzoquinones / Q000378:metabolism; D002417:Cattle; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology*; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D008027:Light; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism
D016227:Benzoquinones; C000607508:DH-I-180-3; D011838:Radiation-Sensitizing Agents; D009243:NAD; D002734:Chlorophyll; D019802:Succinic Acid; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C032623:pheophorbide a; C034257:duroquinone