Browsing by Subject "Metabolic activity"

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    Metabolic activation of CaMKII by coenzyme A
    (Elsevier, 2013-11-07) McCoy, Francis; Darbandi, Rashid; Lee, Hoi Chang; Bharatham, Kavitha; Moldoveanu, Tudor; Royappa, Grace; Dodd, Keela; Lin, Wenwei; Chen, Si-Ing; Tangallapally, Rajendra P.; Kurokawa, Manabu; Lee, Richard E.; Shelat, Anang; Chen, Taosheng; Green, Douglas R.; Harris, Robert A.; Lin, Sue-Hwa; Fissore, Rafael A.; Colbran, Roger J.; Nutt, Leta K.; Biochemistry & Molecular Biology, School of Medicine
    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.