Toggle Main Menu Toggle Search

Open Access padlockePrints

A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast

Lookup NU author(s): Dr Anna Mitchell, Dr Andrew Schaefer, Dr Margaret Jackson, Professor Doug Turnbull, Professor Robert Taylor

Downloads

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


Abstract

Whereas the majority of disease-related mitochondrial DNA mutations exhibit significant biochemical and clinical heterogeneity, mutations within the mitochondrially encoded human cytochrome b gene (MTCYB) are almost exclusively associated with isolated complex III deficiency in muscle and a clinical presentation involving exercise intolerance. Recent studies have shown that a small number of MTCYB mutations are associated with a combined enzyme complex defect involving both complexes I and III, on account of the fact that an absence of assembled complex III results in a dramatic loss of complex I, confirming a structural dependence between these two complexes. We present the biochemical and molecular genetic studies of a patient with both muscle and brain involvement and a severe reduction in the activities of both complexes I and III in skeletal muscle due to a novel mutation in the MTCYB gene that predicts the substitution (Arg318Pro) of a highly conserved amino acid. Consistent with the dramatic biochemical defect, Western blotting and BN-PAGE experiments demonstrated loss of assembled complex I and III subunits. Biochemical studies of the equivalent amino-acid substitution (Lys319Pro) in the yeast enzyme showed a loss of enzyme activity and decrease in the steady-state level of bc1 complex in the mutant confirming pathogenicity. © 2005 FEBS.


Publication metadata

Author(s): Blakely EL, Mitchell AL, Fisher N, Meunier B, Nijtmans LG, Schaefer AM, Jackson MJ, Turnbull DM, Taylor RW

Publication type: Article

Publication status: Published

Journal: FEBS Journal

Year: 2005

Volume: 272

Issue: 14

Pages: 3583-3592

ISSN (print): 17424-64X

ISSN (electronic): 1742-4658

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/j.1742-4658.2005.04779.x

DOI: 10.1111/j.1742-4658.2005.04779.x

PubMed id: 16008558


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share