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Nat Struct Mol Biol. 2016 May;23(5):441-9. doi: 10.1038/nsmb.3206. Epub 2016 Apr 11.

Mammalian elongation factor 4 regulates mitochondrial translation essential for spermatogenesis.

Gao Y1, Bai X1, Zhang D1,2, Han C2,3, Yuan J4, Liu W1,5, Cao X1,2, Chen Z1, Shangguan F1, Zhu Z5, Gao F2,3, Qin Y1,2.

Author information

1
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
2
University of Chinese Academy of Sciences, Beijing, China.
3
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
4
Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
5
Key Laboratory of Food Nutrition and Safety, Ministry of Education, School of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China.

Abstract

Elongation factor 4 (EF4) is a key quality-control factor in translation. Despite its high conservation throughout evolution, EF4 deletion in various organisms has not yielded a distinct phenotype. Here we report that genetic ablation of mitochondrial EF4 (mtEF4) in mice causes testis-specific dysfunction in oxidative phosphorylation, leading to male infertility. Deletion of mtEF4 accelerated mitochondrial translation at the cost of producing unstable proteins. Somatic tissues overcame this defect by activating mechanistic (mammalian) target of rapamycin (mTOR), thereby increasing rates of cytoplasmic translation to match rates of mitochondrial translation. However, in spermatogenic cells, the mTOR pathway was downregulated as part of the developmental program, and the resulting inability to compensate for accelerated mitochondrial translation caused cell-cycle arrest and apoptosis. We detected the same phenotype and molecular defects in germline-specific mtEF4-knockout mice. Thus, our study demonstrates cross-talk between mtEF4-dependent quality control in mitochondria and cytoplasmic mTOR signaling.

PMID:
27065197
DOI:
10.1038/nsmb.3206
[Indexed for MEDLINE]

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