Mitochondria sensitive to ER Ca²⁺ stores

The endoplasmic reticulum (ER) converses with mitochondria during apoptosis, as reported on page 1115. The article by Breckenridge et al. identifies Ca21 as an interorganellar signal that sensitizes mitochondria to death-inducing injuries.

The link between ER-associated events and mitochondrial remodeling during cell death lies in the BAP31 protein, an integral ER membrane protein that is a target of caspase-8. Previous studies indicated that full-length BAP31 inhibits mitochondrial release of cyt c during apoptosis, whereas overexpression of BAP31's caspase cleavage product, p20, induces cell death. The current study demonstrates that p20 exerts its apoptosis-inducing activity from the ER by inducing mitochondrial fission.

ER and mitochondria were found to communicate through an exchange of Ca²⁺. Expression of p20 induced Ca²⁺ release from the ER and...