Well, this is unexpected! Drosophila mitochondrial translation elongation Factor G1 contains a nuclear localization signal.

Most eukaryote genomes encode two mitochondrial translation elongation factor Gs. I recently had a paper in MBE about the origin and evolution of these factors, and I've blogged about it previously. I spotted a very surprising article in PloS One today: "The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling." For some reason, mtEFG1 is dual targeted to the nucleus as well as the mitochondrion. The localisation signal is proposed to be found at the C terminus, unlike the mitochondrial transit peptide, which is found at the N terminus. The authors suggest a model in which "if mitochondrial ATP synthesis is low or EF-G1 is overexpressed and import of EF-G1 proteins into mitochondria is a limiting step, some EF-G1 proteins can accumulate outside of mitochondria and translocate into the nucleus, where they inhibit cellular growth and proliferation."

The authors carry out mutagenesis and subcellular localization analysis of mtEFG1, and find that although the Drosophila mtEFG1 gene is essential, it's not required in every tissue. This leads them to suggest that in some tissues, mtEFG2 and not mtEFG1 is the primary translocation factor. This would be very unexpected as neither spirochete or human spd/mtEFG2 can not promote translocation, and instead spd/mtEFG2 is proposed to be specialised for EF-G's role in ribosome recycling. Additionally, the alignment in my paper shows mtEFG2s don't have the conserved amino acids involved in translocation functions, such as interaction with peptidyl-tRNA. However intramolecular and ribosome interaction sites are well conserved in mtEFG2, suggesting it maintains EF-G-like structural integrity and ribosome binding abilities. Maybe this is sufficient to promote translocation in some conditions? In fact, even the more distantly related EF-G2 of Thermus, which belongs to a whole other ancient subfamily is capable of translocation, hinting that although classical EF-G is very well conserved at the primary sequence level, at least in some conditions the ribosome can accommodate and translocate with more divergent homologs that maintain an EF-G-like structure.

The model of mtEFG1 subcellular location being related to mitochondrial ATP synthesis proposed by Trivigno and Haerry presents a paradox, which they acknowledge: "If EF-G2 functioned as an elongation factors in tissues like the heart, mitochondrial translation and ATP synthesis would occur at normal levels, and EF-G1 would be imported into mitochondria and not accumulate in the nucleus. On the other hand, in tissues like the liver, where EF-G2 cannot function as an elongation factor, mitochondrial translation would decrease, ATP levels would drop, EF-G1 import into mitochondria would decrease and accumulation in the nucleus increase, which would further exacerbate the problem."


So, in conclusion, it's all rather surprising and the model just doesn't seem quite right... it's all very well for a bioinformatician to say this I know, but more experiments needed!

Refs

Atkinson GC, & Baldauf SL (2011). Evolution of elongation factor g and the origins of mitochondrial and chloroplast forms. Molecular biology and evolution, 28 (3), 1281-92 PMID: 21097998

Trivigno C, & Haerry TE (2011). The Drosophila Mitochondrial Translation Elongation Factor G1 Contains a Nuclear Localization Signal and Inhibits Growth and DPP Signaling. PloS one, 6 (2) PMID: 21364917

Tsuboi, M., Morita, H., Nozaki, Y., Akama, K., Ueda, T., Ito, K., Nierhaus, K., & Takeuchi, N. (2009). EF-G2mt Is an Exclusive Recycling Factor in Mammalian Mitochondrial Protein Synthesis Molecular Cell, 35 (4), 502-510 DOI: 10.1016/j.molcel.2009.06.028

Connell, S., Takemoto, C., Wilson, D., Wang, H., Murayama, K., Terada, T., Shirouzu, M., Rost, M., Schüler, M., & Giesebrecht, J. (2007). Structural Basis for Interaction of the Ribosome with the Switch Regions of GTP-Bound Elongation Factors Molecular Cell, 25 (5), 751-764 DOI: 10.1016/j.molcel.2007.01.027