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© The Rockefeller University Press, 0021-9525/2003/3/981-b $5.00
The Journal of Cell Biology, Volume 160, Number 7, 981-b-981

Mitochondria sensitive to ER Ca²⁺ stores

Cleavage of BAP31 causes mitochondria (red) to take up ER- released Ca2+ and then recruit Drp1 (green).

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 near simultaneous Ca²⁺ uptake into the mitochondria. The high mitochondrial Ca²⁺ levels recruited a dynamin- related protein called Drp1, which is known to effect fission. The resulting fragmentation sensitized mitochondria to downstream caspase-8 activities that cause cyt c release. Compared with caspase-8 action alone, the addition of p20 increased cyt c release several fold in vivo. Although isolated mitochondria readily release cyt c in response to caspase signals alone, mitochondria in intact cells may have structural differences that require priming by Drp1 for efficient release of cyt c.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 763K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?