Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2

Leta K. Nutt, Seth Shatkin Margolis, Mette Jensen, Catherine E. Herman, William G. Dunphy, Jeffrey C. Rathmell, Sally Kornbluth

Research output: Contribution to journalArticle

Abstract

Vertebrate female reproduction is limited by the oocyte stockpiles acquired during embryonic development. These are gradually depleted over the organism's lifetime through the process of apoptosis. The timer that triggers this cell death is yet to be identified. We used the Xenopus egg/oocyte system to examine the hypothesis that nutrient stores can regulate oocyte viability. We show that pentose-phosphate-pathway generation of NADPH is critical for oocyte survival and that the target of this regulation is caspase-2, previously shown to be required for oocyte death in mice. Pentose-phosphate-pathway-mediated inhibition of cell death was due to the inhibitory phosphorylation of caspase-2 by calcium/calmodulin-dependent protein kinase II (CaMKII). These data suggest that exhaustion of oocyte nutrients, resulting in an inability to generate NADPH, may contribute to ooctye apoptosis. These data also provide unexpected links between oocyte metabolism, CaMKII, and caspase-2.

Original languageEnglish (US)
Pages (from-to)89-103
Number of pages15
JournalCell
Volume123
Issue number1
DOIs
StatePublished - Oct 7 2005
Externally publishedYes

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Caspase 2
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Phosphorylation
Cell death
Oocytes
Pentoses
Cell Death
NADP
Nutrients
Phosphates
Apoptosis
Calcium-Calmodulin-Dependent Protein Kinases
Pentose Phosphate Pathway
Metabolism
Food
Xenopus
Embryonic Development
Reproduction
Ovum
Vertebrates

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Nutt, L. K., Margolis, S. S., Jensen, M., Herman, C. E., Dunphy, W. G., Rathmell, J. C., & Kornbluth, S. (2005). Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell, 123(1), 89-103. https://doi.org/10.1016/j.cell.2005.07.032

Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. / Nutt, Leta K.; Margolis, Seth Shatkin; Jensen, Mette; Herman, Catherine E.; Dunphy, William G.; Rathmell, Jeffrey C.; Kornbluth, Sally.

In: Cell, Vol. 123, No. 1, 07.10.2005, p. 89-103.

Research output: Contribution to journalArticle

Nutt, LK, Margolis, SS, Jensen, M, Herman, CE, Dunphy, WG, Rathmell, JC & Kornbluth, S 2005, 'Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2', Cell, vol. 123, no. 1, pp. 89-103. https://doi.org/10.1016/j.cell.2005.07.032
Nutt, Leta K. ; Margolis, Seth Shatkin ; Jensen, Mette ; Herman, Catherine E. ; Dunphy, William G. ; Rathmell, Jeffrey C. ; Kornbluth, Sally. / Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. In: Cell. 2005 ; Vol. 123, No. 1. pp. 89-103.
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