1999
DOI: 10.1084/jem.189.2.381
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Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process

Abstract: The barrier function of mitochondrial membranes is perturbed early during the apoptotic process. Here we show that the mitochondria contain a caspase-like enzymatic activity cleaving the caspase substrate Z-VAD.afc, in addition to three biological activities previously suggested to participate in the apoptotic process: (a) cytochrome c; (b) an apoptosis-inducing factor (AIF) which causes isolated nuclei to undergo apoptosis in vitro; and (c) a DNAse activity. All of these factors, which are biochemically disti… Show more

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Cited by 659 publications
(441 citation statements)
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“…Once the mitochondria break, not only the proper mitochondrial function is lost, but also death-promoting proteins, e.g., cytochrome c, apoptosis-inducing factor, or caspases, are released [9,37,38]. Since the release of mitochondrial proteins is observed in both apoptosis and necrosis [3,29,39,40], the shape of death may be decided by downstream events such as caspase activation, while the extent of cell death may be controlled by steps upstream or within mitochondria [36 and references therein].…”
Section: Discussionmentioning
confidence: 99%
“…Once the mitochondria break, not only the proper mitochondrial function is lost, but also death-promoting proteins, e.g., cytochrome c, apoptosis-inducing factor, or caspases, are released [9,37,38]. Since the release of mitochondrial proteins is observed in both apoptosis and necrosis [3,29,39,40], the shape of death may be decided by downstream events such as caspase activation, while the extent of cell death may be controlled by steps upstream or within mitochondria [36 and references therein].…”
Section: Discussionmentioning
confidence: 99%
“…Whereas AIF and Cyt c are considered the prototypic IMS proteins released upon MMP (due to microinjection experiments of recombinant molecules in intact cells, which demonstrated that either proteins suffice to induce the nuclear manifestations of apoptosis [61,62]), several other proteins are released from mitochondria upon OM permeabilization [63,64]. These include but are not limited to adenylate kinase [65], Smac/Diablo [63], Omi/HtrA2 [11,12], EndoG [17] as well as several pro-caspases [66].…”
Section: Detection Of Om Permeabilizationmentioning
confidence: 99%
“…The intermembrane proteins AIF and endonuclease G may act independently of caspase activation (Kuwana and Newmeyer, 2003). According to the cell type, caspases 2, 3, and 9 may be added to the list of mitochondrial intermembrane proteins that enhance the apoptotic process when they are liberated into the cytoplasm (Susin et al, 1999a(Susin et al, , 1999b.…”
mentioning
confidence: 99%