Metabolic Activation of CaMKII by Coenzyme A

Francis McCoy, Rashid Darbandi, HoiChang 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 Harris, Sue Hwa Lin, Rafael A. Fissore, Roger J. Colbran, Leta K. Nutt

Research output: Contribution to journalArticle

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

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinase Type 2
Coenzyme A
Oocytes
Caspase 2
Apoptosis
Calcium-Calmodulin-Dependent Protein Kinases
Xenopus laevis
Calmodulin
Metabolic Activation
Cell Death
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

McCoy, F., Darbandi, R., Lee, H., Bharatham, K., Moldoveanu, T., Grace, C. R., ... 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

Metabolic Activation of CaMKII by Coenzyme A. / McCoy, Francis; Darbandi, Rashid; Lee, HoiChang; Bharatham, Kavitha; Moldoveanu, Tudor; Grace, Christy R.; Dodd, Keela; Lin, Wenwei; Chen, Si Ing; Tangallapally, Rajendra P.; Kurokawa, Manabu; Lee, Richard E.; Shelat, Anang A.; Chen, Taosheng; Green, Douglas R.; Harris, Robert; Lin, Sue Hwa; Fissore, Rafael A.; Colbran, Roger J.; Nutt, Leta K.

In: Molecular Cell, Vol. 52, No. 3, 07.11.2013, p. 325-339.

Research output: Contribution to journalArticle

McCoy, F, Darbandi, R, Lee, H, 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, R, Lin, SH, Fissore, RA, Colbran, RJ & Nutt, LK 2013, 'Metabolic Activation of CaMKII by Coenzyme A', Molecular Cell, vol. 52, no. 3, pp. 325-339. https://doi.org/10.1016/j.molcel.2013.08.043
McCoy F, Darbandi R, Lee H, Bharatham K, Moldoveanu T, Grace CR et al. Metabolic Activation of CaMKII by Coenzyme A. Molecular Cell. 2013 Nov 7;52(3):325-339. https://doi.org/10.1016/j.molcel.2013.08.043
McCoy, Francis ; Darbandi, Rashid ; Lee, HoiChang ; Bharatham, Kavitha ; Moldoveanu, Tudor ; Grace, Christy R. ; Dodd, Keela ; Lin, Wenwei ; Chen, Si Ing ; Tangallapally, Rajendra P. ; Kurokawa, Manabu ; Lee, Richard E. ; Shelat, Anang A. ; Chen, Taosheng ; Green, Douglas R. ; Harris, Robert ; Lin, Sue Hwa ; Fissore, Rafael A. ; Colbran, Roger J. ; Nutt, Leta K. / Metabolic Activation of CaMKII by Coenzyme A. In: Molecular Cell. 2013 ; Vol. 52, No. 3. pp. 325-339.
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