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Inactivation of mitochondrial electron transport by photosensitization of a pheophorbide a derivative.

Molecules and cells (2004-06-05)
Chang Su Kim, Chang-Hee Lee, Phil Ho Lee, Sanghwa Han
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Duroquinone, 97%
Supelco
Duroquinone, Standard for quantitative NMR, TraceCERT®