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.