Metabolic Activation of CaMKII by Coenzyme A

• DOI: 10.1016/j.molcel.2013.08.043
• Publication Date: 2013-10-03T17:15:42Z
• Authors: Francis McCoy; Rashid Darbandi; Hoi Chang Lee; Kavitha Bharatham; Tudor Moldoveanu; Christy R. Grace; Keela Dodd; Wenwei Lin; Si-Ing Chen; Rajendra P. Tanga...; Manabu Kurokawa; Richard E. Lee; Anang A. Shelat; Taosheng Chen; Douglas R. Green; Robert A. Harris; Sue-Hwa Lin; Rafael A. Fissore; Roger J. Colbran; Leta K. Nutt
• Keywords: Oocyte cell death; Transcriptional Activation; 0303 health sciences; Cell Survival; Caspase 2; Gene Expression Regulation, Developmental; Calcium/calmodulin-dependent protein kinase II; Apoptosis; Cell Biology; Mice; Xenopus laevis; 03 medical and health sciences; Metabolic activity; Oocytes; Animals; Coenzyme A; Phosphorylation; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Molecular Biology; Protein Binding; Signal Transduction

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.