Metabolic regulation of apoptosis via coenzyme A mediated activation of CaMKII (577.2)

The metabolic status of a cell is a fundamentally important factor in deciding whether or not a cell engages its apoptotic machinery. We have previously shown that active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII) mediated phosphorylation of caspase-2(1) but the link between metabolic activity and CaMKII is poorly understood. In this study(2) 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; effectively lowering the activation threshold of CaMKII for Ca2+/calmodulin. 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 oocyt...