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Metabolic activation of CaMKII by coenzyme A.

Molecular cell (2013-10-08)
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
PMID24095281
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 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.

MATERIALS
Product Number
Brand
Product Description
C4282
Sigma-Aldrich
Coenzyme A hydrate, ≥85% (UV, HPLC)