Identification of porin specifically expressed in tumor cells and its application for development of anti-tumor drugs

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First of all, to understand the physiological meanings of hexokinase binding to mitochondria observed in tumor cells, we isolated and characterized tumor mitochondria. As a result, mitochondria-bound hexokinase was found to use mitochondrial ATP preferentially than thatsynthesized in cytosol. Furthermore, this binding was found to enable the efficient cross talk between glycolysis and oxydative phosphorylation.Next, to understand the molecular mechanisms of hexokinase binding to mitocondrial membrane, we tried to identify the porin isoform (s) expressed as binding site (s) of hexokinase in tumor mitochondria. As a result,1) we succeeded to isolate two kinds of cDNA clones expressed in AH130 cells2) these cDNA clones were found to encode two kinds of porin isoform called as VDAC1 and VDAC23) furthermore, both of VDAC1 and VDAC2 were found to be expressed in mitochondrial membrane.