Release of adenylate kinase 2 from the mitochondrial intermembrane space during apoptosis

The release of two mitochondrial proteins, cytochrome c and apoptosis-induc ing factor (AIF), into the soluble cytoplasm of cells undergoing apoptosis is well established. Using spectrophotometric determination of enzyme activ ity, the accumulation of adenylate kinase (AK) activity in the cytosolic fr action of apoptotic cells has also been observed recently. However, three i sozymes, AK1, AK2 and AK3, have been characterized in mammalian cells and s hown to be localized in the cytosol, mitochondrial intermembrane space and mitochondrial matrix, respectively, and it is unknown which one of these is ozymes accumulates in the cytosol during apoptosis, We now demonstrate that in apoptotic cells only AK2 was translocated into the cytosol concomitantl y with cytochrome c, The amount of AK1 in cytosol, as well as the amount of matrix-associated AK3, remained unchanged during the apoptotic process. Th us, our data suggest that only intermembrane proteins are released from mit ochondria during the early phase of the apoptotic process. (C) 1999 Federat ion of European Biochemical Societies.