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Metabolic activation of CaMKII by coenzyme A.

ABSTRACT: Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation of caspase-2, but the link between metabolic activity and CaMKII is poorly understood. Here we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis by directly activating CaMKII. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca(2+) to activate CaMKII in a calmodulin-dependent manner. Furthermore, we show that CoA inhibits apoptosis not only in X. laevis oocytes but also in Murine oocytes. These findings uncover a direct mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability.

SUBMITTER: McCoy F

PROVIDER: S-EPMC3967247 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Metabolic activation of CaMKII by coenzyme A.

McCoy Francis F Darbandi Rashid R Lee Hoi Chang HC Bharatham Kavitha K Moldoveanu Tudor T Grace Christy R CR Dodd Keela K Lin Wenwei W Chen Si-Ing SI Tangallapally Rajendra P RP Kurokawa Manabu M Lee Richard E RE Shelat Anang A AA Chen Taosheng T Green Douglas R DR Harris Robert A RA Lin Sue-Hwa SH Fissore Rafael A RA Colbran Roger J RJ Nutt Leta K LK

Molecular cell 20131003 3

Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation of caspase-2, but the link between metabolic activity and CaMKII is poorly understood. Here we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis by directly activating CaMKII. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca(2+) to activate CaMKII in a calmodulin-dependent manner. ...[more]

PMID: 24095281

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