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.