Caspase cleavage product of XXXX induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing @entity4674 release to the cytosol.

@entity1949 @entity25490 @entity4674 @entity24366 @entity8186 @entity141 @entity9289
Stimulation of cell surface death receptors activates @entity8186 , which targets a limited number of substrates including @entity24366 , an integral membrane protein of the endoplasmic reticulum (ER). Recently, we reported that a caspase-resistant @entity24366 mutant inhibited several features of Fas-induced apoptosis, including the release of @entity4674 ( @entity4674 ) from mitochondria (Nguyen, M., D.G. Breckenridge, A. Ducret, and G.C. Shore. 2000. Mol. Cell. Biol. 20:6731-6740), implicating ER-mitochondria crosstalk in this pathway. Here, we report that the @entity9289 caspase cleavage fragment of @entity24366 can direct pro-apoptotic signals between the ER and mitochondria. Adenoviral expression of @entity9289 caused an early release of @entity141 from the ER, concomitant uptake of @entity141 into mitochondria, and mitochondrial recruitment of @entity25490 , a dynamin-related protein that mediates scission of the outer mitochondrial membrane, resulting in @entity1949 and fission of the mitochondrial network. Inhibition of @entity25490 or ER-mitochondrial @entity141 signaling prevented @entity9289 -induced fission of mitochondria. @entity9289 strongly sensitized mitochondria to @entity8186 -induced @entity4674 release, whereas prolonged expression of @entity9289 on its own ultimately induced caspase activation and apoptosis through the mitochondrial apoptosome stress pathway. Therefore, @entity8186 cleavage of @entity24366 at the ER stimulates @entity141 -dependent mitochondrial fission, enhancing the release of @entity4674 in response to this initiator caspase.
