Journal article

Mutations in MTFMT Underlie a Human Disorder of Formylation Causing Impaired Mitochondrial Translation

Elena J Tucker, Steven G Hershman, Caroline Koehrer, Casey A Belcher-Timme, Jinal Patel, Olga A Goldberger, John Christodoulou, Jonathon M Silberstein, Matthew McKenzie, Michael T Ryan, Alison G Compton, Jacob D Jaffe, Steven A Carr, Sarah E Calvo, Uttam L RajBhandary, David R Thorburn, Vamsi K Mootha



The metazoan mitochondrial translation machinery is unusual in having a single tRNA(Met) that fulfills the dual role of the initiator and elongator tRNA(Met). A portion of the Met-tRNA(Met) pool is formylated by mitochondrial methionyl-tRNA formyltransferase (MTFMT) to generate N-formylmethionine-tRNA(Met) (fMet-tRNA(met)), which is used for translation initiation; however, the requirement of formylation for initiation in human mitochondria is still under debate. Using targeted sequencing of the mtDNA and nuclear exons encoding the mitochondrial proteome (MitoExome), we identified compound heterozygous mutations in MTFMT in two unrelated children presenting with Leigh syndrome and combined O..

View full abstract


Awarded by National Institutes of Health


Funding Acknowledgements

We thank J. Silke and P. Ekert for providing the pF_5x_UAS_MCS_SV40_puroGEV16-W vector, C. Guiducci, C. Sougnez, L. Ambrogia, and J. Wilkinson, for assistance with sample preparation and sequencing, T. Fennel, M. DePristo, E. Banks, and K. Garimella for assistance with bioinformatic analysis, S. Flynn for assistance with IRBs, and the subjects and referring physicians who participated in the study. This work was supported by an Australian Postgraduate Award to E.J.T., a National Defense Science and Engineering Graduate Fellowship to S.G.H., an Australian National Health and Medical Research Council (NHMRC) Career Development Award to M.M., an NHMRC Principal Research fellowship to D.R.T., the Victorian Government's Operational Infrastructure Support Program, and grants from the Ramaciotti Foundation and the James and Vera Lawson Trust to M.M., the NHMRC to MM., M.T.R. and D.R.T., and the National Institutes of Health to U.L.R. (GM17151) and to V.K.M. (GM077465 and GM097136).