Toggle Main Menu Toggle Search

Open Access padlockePrints

Mutations in C12orf65 in Patients with Encephalomyopathy and a Mitochondrial Translation Defect

Lookup NU author(s): Professor Zofia Chrzanowska-Lightowlers

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

We investigated the genetic basis for a global and uniform decrease in mitochondrial translation in fibroblasts from patients in two unrelated pedigrees who developed Leigh syndrome, optic atrophy, and ophthalmoplegia. Analysis of the assembly of the oxidative phosphorylation complexes showed severe decreases of complexes I, IV, and V and a smaller decrease in complex III. The steady-state levels of mitochondrial mRNAs, tRNAs, and rRNAs were not reduced, nor were those of the mitochondrial translation elongation factors or the protein components of the mitochondrial ribosome. Using homozygosity mapping, we identified a 1 bp deletion in C12orf65 in one patient, and DNA sequence analysis showed a different 1 bp deletion in the second patient. Both mutations predict the same premature stop codon. C12orf65 belongs to a family of four mitochondrial class I peptide release factors, which also includes mtRF1a, mtRF1, and Ict1, all characterized by the presence of a GGQ motif at the active site. However, C12orf65 does not exhibit peptidyl-tRNA hydrolase activity in an in vitro assay with bacterial ribosomes. We suggest that it might play a role in recycling abortive peptidyl-tRNA species, released from the ribosome during the elongation phase of translation.


Publication metadata

Author(s): Antonicka H, Ostergaard E, Sasarman F, Weraarpachai W, Wibrand F, Pedersen AM, Rodenburg RJ, vanderKnaap MS, Smeitink JA, Chrzanowska-Lightowlers ZMA, Shoubridge EA

Publication type: Article

Publication status: Published

Journal: American Journal of Human Genetics

Year: 2010

Volume: 87

Issue: 1

Pages: 115-122

Print publication date: 09/07/2010

ISSN (print): 0002-9297

ISSN (electronic): 1537-6605

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.ajhg.2010.06.004

DOI: 10.1016/j.ajhg.2010.06.004


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share