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Metabolic activation of CaMKII by coenzyme A

By Francis McCoy, Rashid Darbandi, Hoi Chang Lee, Kavitha Bharatham, Tudor Moldoveanu, Grace Royappa, Keela Dodd, Wenwei Lin, Si-Ing Chen, Rajendra P. Tangallapally, Manabu Kurokawa, Richard E. Lee, Anang Shelat, Taosheng Chen, Douglas R. Green, Robert A. Harris, Sue-Hwa Lin, Rafael A. Fissore, Roger J. Colbran and Leta K. Nutt

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

Topics: Calcium/calmodulin-dependent protein kinase II, Oocyte cell death, Metabolic activity
Publisher: Elsevier
Year: 2013
DOI identifier: 10.1016/j.molcel.2013.08.043
OAI identifier: oai:scholarworks.iupui.edu:1805/6898
Provided by: IUPUIScholarWorks

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