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McCoy F, Darbandi R, Lee HC, Bharatham K, Moldoveanu T, Grace CR, Dodd K, Lin W, Chen SI, Tangallapally RP, Kurokawa M, Lee RE, Shelat AA, Chen T, Green DR, Harris RA, Lin SH, Fissore RA, Colbran RJ, Nutt LK.
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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.
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