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Metabolic regulation of apoptosis via coenzyme A mediated activation of CaMKII (577.2)
Author(s) -
McCoy Francis,
Darbandi Rashid,
Lee Hoi Chang,
Bharatham Kavitha,
Moldoveanu Tudor,
Grace Christy,
Dodd Keela,
Lin Wenwei,
Chen SiIng,
Tangallapally Rajendra,
Kurokawa Manabu,
Lee Richard,
Shelat Anang,
Chen Taosheng,
Green Douglas,
Harris Robert,
Lin SueHwa,
Fissore Rafael,
Colbran Roger,
Nutt Leta
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.577.2
Subject(s) - apoptosis , microbiology and biotechnology , chemistry , biochemistry , biology
The metabolic status of a cell is a fundamentally important factor in deciding whether or not a cell engages its apoptotic machinery. We have previously shown that active metabolism regulates oocyte cell death via calcium/calmodulin‐dependent protein kinase II (CaMKII) mediated phosphorylation of caspase‐2 (1) but the link between metabolic activity and CaMKII is poorly understood. In this study (2) we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis, in a novel mechanism of CaMKII activation. 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; effectively lowering the activation threshold of CaMKII for Ca 2+ /calmodulin. Furthermore, we show that CoA inhibits apoptosis not only in X. laevis oocytes, but also in Murine oocytes. These findings uncover a novel mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability, and regulating apoptosis.Grant Funding Source : Supported by the V Foundation, ALSAC, and NIH