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

doi:10.1016/j.molcel.2013.08.043

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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 language	English (US)
Pages (from-to)	325-339
Number of pages	15
Journal	Molecular cell
Volume	52
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2013.08.043
State	Published - Nov 7 2013
Externally published	Yes

Funding

The authors would like to thank Dr. Sara Gragg for her support and guidance, and Changli He for technical support. This work was supported by the V Foundation, the American Lebanese Syrian Associated Charities (ALSAC), and the National Cancer Institute of the National Institutes of Health under award number P30CA021765. R.J.C. was supported by NIH award R01MH063232. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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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

@article{d59ef779844b49eba7e6fcee04e820e1,

title = "Metabolic Activation of CaMKII by Coenzyme A",

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.",

author = "Francis McCoy and Rashid Darbandi and Lee, {Hoi Chang} and Kavitha Bharatham and Tudor Moldoveanu and Grace, {Christy R.} and Keela Dodd and Wenwei Lin and Chen, {Si Ing} and Tangallapally, {Rajendra P.} and Manabu Kurokawa and Lee, {Richard E.} and Shelat, {Anang A.} and Taosheng Chen and Green, {Douglas R.} and Harris, {Robert A.} and Lin, {Sue Hwa} and Fissore, {Rafael A.} and Colbran, {Roger J.} and Nutt, {Leta K.}",

note = "Funding Information: The authors would like to thank Dr. Sara Gragg for her support and guidance, and Changli He for technical support. This work was supported by the V Foundation, the American Lebanese Syrian Associated Charities (ALSAC), and the National Cancer Institute of the National Institutes of Health under award number P30CA021765. R.J.C. was supported by NIH award R01MH063232. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ",

year = "2013",

month = nov,

day = "7",

doi = "10.1016/j.molcel.2013.08.043",

language = "English (US)",

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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 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

TY - JOUR

T1 - Metabolic Activation of CaMKII by Coenzyme A

AU - McCoy, Francis

AU - Darbandi, Rashid

AU - Lee, Hoi Chang

AU - Bharatham, Kavitha

AU - Moldoveanu, Tudor

AU - Grace, Christy R.

AU - Dodd, Keela

AU - Lin, Wenwei

AU - Chen, Si Ing

AU - Tangallapally, Rajendra P.

AU - Kurokawa, Manabu

AU - Lee, Richard E.

AU - Shelat, Anang A.

AU - Chen, Taosheng

AU - Green, Douglas R.

AU - Harris, Robert A.

AU - Lin, Sue Hwa

AU - Fissore, Rafael A.

AU - Colbran, Roger J.

AU - Nutt, Leta K.

N1 - Funding Information: The authors would like to thank Dr. Sara Gragg for her support and guidance, and Changli He for technical support. This work was supported by the V Foundation, the American Lebanese Syrian Associated Charities (ALSAC), and the National Cancer Institute of the National Institutes of Health under award number P30CA021765. R.J.C. was supported by NIH award R01MH063232. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

PY - 2013/11/7

Y1 - 2013/11/7

N2 - 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.

AB - 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.

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VL - 52

SP - 325

EP - 339

JO - Molecular cell

JF - Molecular cell

IS - 3

ER -

Metabolic Activation of CaMKII by Coenzyme A

Abstract

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ASJC Scopus subject areas

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