Irreversible conversion of xanthine dehydrogenase into xanthine oxidase bya mitochondrial protease

Irreversible conversion of xanthine dehydrogenase (XDH) to its oxygen free radical producing oxidase (XO) form occurs through an uncharacterized prote olytic process, which was studied in human liver. Upon incubation of fresh unfrozen liver cytosol, XDH remained intact. When recombinant human XDH was coincubated with subcellular fractions of human liver, the mitochondrial i ntermembrane space was shown to contain a heat-labile activity that convert ed XDH irreversibly to XO. This activity is resistant to inhibitors of all major groups of proteases, We postulate that this novel type of proteolytic enzyme is released into the cytosol upon mitochondrial damage. (C) 1999 Fe deration of European Biochemical Societies.