ENZYME-RELEASE FROM MITOCHONDRIA DURING REOXYGENATION OF RAT-LIVER

Reoxygenation-induced release of mitochondrial aspartate aminotransfer ase (mAST) into the cytosol was studied using perfused rat liver. As t he absolute activity of mAST in the perfusate did not indicate the deg ree of mitochondrial enzyme release, the following 3 methods were appl ied: measurement of the mAST to total AST ratio in the efferent perfus ate, the digitonin infusion method, and measurement of mAST activity i n the cytosolic compartment isolated from perfused livers. The results by all 3 methods were consistent and showed that mitochondrial injury occurs on reoxygenation. The mitochondrial Ca2+ content was proportio nal to the extent of mAST release during reoxygenation, indicating inv olvement of Ca2+ in the enzyme release. CsA, a potent inhibitor of Ca2 +-induced increase in permeability of the mitochondrial membrane, comp letely prevented mAST release on reoxygenation. We conclude that durin g reoxygenation of hypoxic liver, mAST leaks into the cytosol in a Ca2 +-dependent, CsA-sensitive manner.