Introduction
Most eukaryotic cells contain abundant mitochondria, the double membrane-bound, dynamic and complex organelles that take up approximately 25% of the cytoplasmic volume, and are the key sites for cellular energy production(1 ). In addition to its essential role in generating energy, mitochondria are malleable structures intimately involved in an assortment of cellular processes including cellular redox regulation, cell signaling, calcium homeostasis, cell cycle, cell survival and death; thus, the functions of mitochondria are vital to health and lifespan.(2-5 ) Importantly, to maintain their size, shape, number and function, mitochondria continuously undergo morphologically dynamic processes of fusion and fission.(6 ) While fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a way of complementation, fission generates new mitochondria and contributes to quality control by enabling the removal of damaged mitochondria. Under high cellular stress, fission can also promote apoptosis. (7, 8 ) Therefore, mitochondrial dynamics is critical in controlling the quality of this vital organelle and in ensuring proper inheritance and distribution of mitochondria. Both fission and fusion are highly regulated through their respective machinery.
Eukaryotic elongation factor-2 (eEF2), encoded by EEF2 gene that localizes on chromosome 19 in humans and a monomeric protein of 858 amino acid residues, is a key regulator of protein synthesis.(9 ) eEF2 belongs to the G protein family, and undergoes conformational changes upon binding to a guanosine nucleotide.(10 ) In the translocation process of peptide-tRNA from the ribosomal A-site to P-site, the eEF2-complexed GTP is hydrolyzed and then eEF2 leaves the ribosome as inactive eEF2-GDP.(10 ) eEF2 catalyzes the GTP-dependent ribosomal translocation during elongation and during this step, the ribosome changes from the pre-translocational to the post-translocational state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively.(11 ) The activity of eEF2 is regulated by eEF2 kinase, an enzyme phosphorylates eEF2 on Thr-56, and phosphorylation of eEF2 reduces its binding affinity to the ribosome, thus inhibiting mRNA translation. Here, we report a previously unrecognized but important function of eEF2 in regulating mitochondrial fission. We demonstrated that eEF2 is present in the mitochondria as well as in the cytoplasm and supports mitochondrial fission through binding to dynamin-related protein 1 (Drp1) and activating its GTPase activity. The current study not only reveals a novel biological function of eEF2, but also provides a new regulatory pathway of the mitochondrial dynamics.