抄録
It is now well established that the mitochondria play an important role in the regulation of apoptotic cell death by mechanisms which have been conserved during evolution. Thus, it seems that a host of lethal agents target the mitochondria and stimulate their release of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and other parts of the apoptotic process. Cytochrome c release is governed by the Bcl-2 family of proteins and occurs by a two-step process, which is initiated by dissociation of the hemoprotein from cardiolipin, the phospholipid that anchors it to the outer surface of the inner mitochondrial membrane. The dissociation of cytochrome c from cardiolipin is promoted by pro-oxidants and inhibited by glutaredoxin-2 and other mitochondrial antioxidant enzymes. Release of the solubilized pool of cytochrome c into the cytosol may then occur by pore formation mediated by pro-apoptotic Bcl-2 family proteins, notably Bax and Bak, or by Ca2+-triggered mitochondrial permeability transition. In both cases, there seems to be a role for voltage dependent anion channels (VDAC) in the outer mitochondrial membrane, and our recent findings suggest that VDAC located in the plasma membrane of apoptotic cells may also be important for cell death mediated by the mitochondrial pathway. Taken together, these findings have further emphasized the critical role of the mitochondria in the regulation of cell life and death. [Jpn J Physiol 54 Suppl:S28 (2004)]
