Germline quality control: eEF2K stands guard to eliminate defective oocytes
Journal
Developmental cell
Journal Volume
28
Journal Issue
5
Pages
561-572
Date Issued
2014-03-10
Author(s)
Liao, Yi
Novak, James S
Hu, Zhixian
Merkin, Jason J
Shymkiv, Yuriy
Braeckman, Bart P
Dorovkov, Maxim V
Nguyen, Alexandra
Clifford, Peter M
Nagele, Robert G
Harrison, David E
Ellis, Ronald E
Ryazanov, Alexey G
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.
SDGs
Other Subjects
elongation factor 2 kinase; FLICE inhibitory protein; X linked inhibitor of apoptosis; animal cell; animal tissue; apoptosis; article; Caenorhabditis elegans; cell death; controlled study; embryo; embryo death; enzyme activity; enzyme regulation; female; germ line; mouse; nonhuman; oocyte; oxidative stress; priority journal; protein function; protein synthesis inhibition; quality control; Caenorhabditis elegans; Mus; Animals; Apoptosis; Blotting, Western; Caenorhabditis elegans; Caspases; Cells, Cultured; Elongation Factor 2 Kinase; Embryo, Mammalian; Female; Fibroblasts; Germ Cells; Immunoenzyme Techniques; In Situ Nick-End Labeling; Male; Mice; Mice, Knockout; NIH 3T3 Cells; Oocytes; Ovary; Phosphorylation; Quality Control
Publisher
CELL PRESS
Type
journal article
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