Nuclear Apaf-1 and cytochrome c redistribution following stress-induced apoptosis

Apoptotic protease activating factor-1 (Apaf-1) and cytochrome a are cofactors critical for inducing caspase-9 activation following stress-induced apoptosis. One consequence of caspase-9 activation is nuclear-cytoplasmic barrier disassembly, which is required for nuclear caspase-3 translocation. In the nucleus, caspase-3 triggers proteolysis of the caspase-activated DNA nuclease (CAD) inhibitor, causing CAD induction and subsequent DNA degradation. Here we demonstrate that apoptotic cells show perinuclear cytochrome c aggregation, which may be critical for nuclear redistribution of cytochrome c and Apaf-1. We thus indicate that the nuclear redistribution of these cofactors concurs with the previously reported caspase-9-induced nuclear disassembly, and may represent an early apoptotic hallmark. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.