Genetics of Apoptosis

(Barry) #1

induced by stress originating outside the ER. The massive surface area of ER
membranes might provide a platform for the concentration and assembly of
complexes that regulate activation of caspases, including caspase-12 and
procaspase-8L. In addition, it is possible that Bcl-2 family members create pores in
the ER membrane, releasing chaperones from the lumen that regulate caspase
activation or other steps in the execution phase. Indeed, swelling and dilation of the
ER is common during apoptosis (Weller et al., 1995; Wu et al., 1999; Chang et a/.,
2000; Herrera et al., 2000; Muriel et al., 2000; Zeng and Xu, 2000), suggesting that
ion homeostasis and volume control are deregulated. Unfortunately, elucidation of
ER-controlled processes in apoptosis may be a slow process, since at present there is
no assay (aside from calcium release) to measure changes in the organelle during cell
death. In retrospect, this leads one to ask: what would our current knowledge of the
involvement of mitochondria in apoptosis be had Cyt.c not been discovered as a
cytosolic factor required for caspase activation in vitro?


THE ROLE OF THE ENDOPLASMIC RETICULUM IN APOPTOSIS 119
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