SUMMARY 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, in a novel mechanism of CaMKII activation. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca2+ 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 novel mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability.

Background:In the basal state, oocytes produce lactate from G6P even in the presence of oxygen. Results: Addition of G6P to egg extracts inhibits PP1, preventing dephosphorylation/inactivation of CaMKII and initiation of apoptotic pathways. Conclusion: Normal oocyte metabolism suppresses apoptosis by inhibiting PP1 and activating CaMKII. Significance: These mechanistic insights suggest potential targets for modulating cell death.

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