Mitochondrial EF4 links respiratory dysfunction and

cytoplasmic translation in Caenorhabditis elegans

Biochimica et Biophysica Acta(2014)， Received 12 November 2013, Accepted 9 May 2014, Published online 15 May 2014

Mitochondrial EF4 links respiratory dysfunction and cytoplasmic translation in Caenorhabditis

Fang Yang, Yanyan Gao , Zhikai Li , Luming Chen , Zhiping Xia , Tao Xu , Yan QinAbstract: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.