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Colbran Lab

Metabolic activation of CaMKII by coenzyme A.

AUTHORS

McCoy FFrancis , Darbandi R Rashid , Lee HC Hoi Chang , Bharatham K Kavitha , Moldoveanu T Tudor , Grace CR Christy R , Dodd K Keela , Lin W Wenwei , Chen SI Si-Ing , Tangallapally RP Rajendra P , Kurokawa M Manabu , Lee RE Richard E , Shelat AA Anang A , Chen T Taosheng , Green DR Douglas R , Harris RA Robert A , Lin SH Sue-Hwa , Fissore RA Rafael A , Colbran RJ Roger J , Nutt LK Leta K . Molecular cell. 2013 11 7; 52(3). 325-39

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.