Germline Quality Control: EEF2K Stands Guard to Eliminate Defective Oocytes

Hsueh Ping Chu, Yi Liao, James S. Novak, Zhixian Hu, Jason J. Merkin, Yuriy Shymkiv, Bart P. Braeckman, Maxim V. Dorovkov, Alexandra Nguyen, Peter M. Clifford, Robert G. Nagele, David E. Harrison, Ronald E. Ellis, Alexey G. Ryazanov

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The control of germline quality is critical to reproductive success and survival of a species; however, the mechanisms underlying this process remain unknown. Here, we demonstrate that elongation factor 2 kinase (eEF2K), an evolutionarily conserved regulator of protein synthesis, functions to maintain germline quality and eliminate defective oocytes. We show that disruption of eEF2K in mice reduces ovarian apoptosis and results in the accumulation of aberrant follicles and defective oocytes at advanced reproductive age. Furthermore, the loss of eEF2K in Caenorhabditis elegans results in a reduction of germ cell death and significant decline in oocyte quality and embryonic viability. Examination of the mechanisms by which eEF2K regulates apoptosis shows that eEF2K senses oxidative stress and quickly downregulates short-lived antiapoptotic proteins, XIAP and c-FLIPL by inhibiting global protein synthesis. These results suggest that eEF2K-mediated inhibition of protein synthesis renders cells susceptible to apoptosis and functions to eliminate suboptimal germ cells.

Original languageEnglish (US)
Pages (from-to)561-572
Number of pages12
JournalDevelopmental Cell
Volume28
Issue number5
DOIs
StatePublished - Mar 10 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Germline Quality Control: EEF2K Stands Guard to Eliminate Defective Oocytes'. Together they form a unique fingerprint.

Cite this