Protoporphyrin IX binding and transport by recombinant mouse PBR

The mitochondrial 18 kDa peripheral-type benzodiazepine receptor (PBR), a high affinity cholesterol binding protein, has been shown to interact with protoporphyrin IX (PPIX) and this interaction was assumed to be involved in the regulation of heme biosynthesis and porphyrin-based photodynamic therapy in cancer. In order to test this hypothesis recombinant mouse PBR was expressed in Escherichia coli. The recombinant gene product showed in E coli protoplasts specific affinity for PPIX binding. PPIX could displace PK 11195 binding. Moreover, induced PBR protein expression in E coli protoplasts caused an uptake of PPIX that could be completely inhibited by cholesterol and to a lesser extent inhibited by PK 11195 and Ro5-4864. These results suggest that PBR, in addition to its role in cholesterol and coproporphyrinogen III transport, is also directing the mitochondrial PPIX import, a function that can be ascribed to the 18 kDa PBR protein alone. (C) 2003 Elsevier Inc. All rights reserved.