Metabolic Activation of CaMKII by Coenzyme A

Francis McCoy, Rashid Darbandi, Hoi Chang Lee, Kavitha Bharatham, Tudor Moldoveanu, Christy R. Grace, Keela Dodd, Wenwei Lin, Si Ing Chen, Rajendra P. Tangallapally, 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

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Abstract

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 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 direct mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability.

Original languageEnglish (US)
Pages (from-to)325-339
Number of pages15
JournalMolecular Cell
Volume52
Issue number3
DOIs
StatePublished - Nov 7 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

McCoy, F., Darbandi, R., Lee, H. C., Bharatham, K., Moldoveanu, T., Grace, C. R., Dodd, K., Lin, W., Chen, S. I., Tangallapally, R. P., Kurokawa, M., Lee, R. E., Shelat, A. A., Chen, T., Green, D. R., Harris, R. A., Lin, S. H., Fissore, R. A., Colbran, R. J., & Nutt, L. K. (2013). Metabolic Activation of CaMKII by Coenzyme A. Molecular Cell, 52(3), 325-339. https://doi.org/10.1016/j.molcel.2013.08.043