McCoy, FrancisDarbandi, RashidLee, Hoi ChangBharatham, KavithaMoldoveanu, TudorRoyappa, GraceDodd, KeelaLin, WenweiChen, Si-IngTangallapally, Rajendra P.Kurokawa, ManabuLee, Richard E.Shelat, AnangChen, TaoshengGreen, Douglas R.Harris, Robert A.Lin, Sue-HwaFissore, Rafael A.Colbran, Roger J.Nutt, Leta K.2015-09-142015-09-142013-11-07McCoy, F., Darbandi, R., Lee, H. C., Bharatham, K., Moldoveanu, T., Royappa, G., … Nutt, L. K. (2013). Metabolic activation of CaMKII by Coenzyme A. Molecular Cell, 52(3), 325–339. http://doi.org/10.1016/j.molcel.2013.08.043https://hdl.handle.net/1805/6898Active 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.en-USPublisher PolicyCalcium/calmodulin-dependent protein kinase IIOocyte cell deathMetabolic activityMetabolic activation of CaMKII by coenzyme AArticle