PHOTOSENSITIZATION OF MITOCHONDRIA BY LIPOSOME-BOUND PORPHYRINS

We have compared the photodynamic activities of hematoporphyrin (HP) a nd protoporphyrin (PP) on isolated rat liver mitochondria by measuring the decline of the respiratory control ratio (RCR) after irradiation at 365 nm. Before addition to the respiratory medium, the dyes were di ssolved in phosphate-buffered saline (PBS) or incorporated into unilam ellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC), sometimes e nriched with cholesterol (Chol) or cardiolipin (Card), which are natur ally present in mitochondrial membranes. Chol and especially Card stro ngly increase the porphyrin uptake by mitochondria. In all experimenta l conditions, PP is taken up by mitochondria to a higher extent than H P. Nevertheless, under conditions giving the same amount of mitochondr ia-bound dye, HP is a more efficient photosensitizer than PP. As the e fficiency of singlet oxygen production has been shown to be equivalent for the two porphyrins in monomeric state, the resulting photobiologi cal effects are explained in terms of different localization of HP and PP in the mitochondrial membranes. In particular, HP preferentially l ocalizes in the protein-rich polar domains of the inner mitochondrial membrane, whereas PP dissolves in the lipid regions of the membranes.