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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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