Mitochondrial EF4 links respiratory dysfunction and cytoplasmic translation in Caenorhabditis elegans.
How animals coordinate cellular bioenergetics in response to stress conditions is an essential question related to aging, obesity and cancer. Elongation factor 4 (EF4/LEPA) is a highly conserved protein that promotes protein synthesis under stress conditions, whereas its function in metazoans remains unknown. Here, we show that, in Caenorhabditis elegans, the mitochondria-localized CeEF4 (referred to as mtEF4) affects mitochondrial functions, especially at low temperature (15°C). At worms' optimum growing temperature (20°C), mtef4 deletion leads to self-brood size reduction, growth delay and mitochondrial dysfunction. Transcriptomic analyses show that mtef4 deletion induces retrograde pathways, including mitochondrial biogenesis and cytoplasmic translation reorganization. At low temperature (15°C), mtef4 deletion reduces mitochondrial translation and disrupts the assembly of respiratory chain supercomplexes containing complex IV. These observations are indicative of the important roles of mtEF4 in mitochondrial functions and adaptation to stressful conditions.
Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Fang
F
Yang
Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Yanyan
Y
Gao
Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Zhikai
Z
Li
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Luming
L
Chen
University of Chinese Academy of Sciences, Beijing 100049, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Zhiping
Z
Xia
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China. Electronic address: xutao@ibp.ac.cn.
Tao
T
Xu
Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China. Electronic address: qiny@ibp.ac.cn.
Yan
Y
Qin
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D017931:DNA Primers; D004579:Electron Transport; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D013696:Temperature
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D024101:Mitochondrial Proteins
C. elegans; EF4(LepA/GUF1); Mitochondrial dysfunction; Retrograde pathways; Translation