Toggle Main Menu Toggle Search

Open Access padlockePrints

Investigating the role of the physiological isoform switch of cytochrome c oxidase subunits in reversible mitochondrial disease

Lookup NU author(s): Dr Veronika Boczonadi, Michele Giunta, Maria Lane, Professor Rita HorvathORCiD


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


Reversible infantile respiratory chain deficiency is characterised by spontaneous recovery of mitochondrial myopathy in infants. We studied whether a physiological isoform switch of nuclear cytochrome c oxidase subunits contributes to the age-dependent manifestation and spontaneous recovery in reversible mitochondrial disease. Some nuclear-encoded subunits of cytochrome c oxidase are present as tissue-specific isoforms. Isoforms of subunits COX6A and COX7A expressed in heart and skeletal muscle are different from isoforms expressed in the liver, kidney and brain. Furthermore, in skeletal muscle both the heart and liver isoforms of subunit COX7A have been demonstrated with variable levels, indicating that the tissue-specific expression of nuclear-encoded subunits could provide a basis for the fine-tuning of cytochrome c oxidase activity to the specific metabolic needs of the different tissues.We demonstrate a developmental isoform switch of COX6A and COX7A subunits in human and mouse skeletal muscle. While the liver type isoforms are more present soon after birth, the heart/muscle isoforms gradually increase around 3 months of age in infants, 4 weeks of age in mice, and these isoforms persist in muscle throughout life. Our data in follow-up biopsies of patients with reversible infantile respiratory chain deficiency indicate that the physiological isoform switch does not contribute to the clinical manifestation and to the spontaneous recovery of this disease. However, understanding developmental changes of the different cytochrome c oxidase isoforms may have implications for other mitochondrial diseases.This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. (C) 2015 Elsevier Ltd. All rights reserved.

Publication metadata

Author(s): Boczonadi V, Giunta M, Lane M, Tulinius M, Schara U, Horvath R

Publication type: Article

Publication status: Published

Journal: International Journal of Biochemistry & Cell Biology

Year: 2015

Volume: 63

Pages: 32-40

Print publication date: 01/06/2015

Online publication date: 07/02/2015

Acceptance date: 29/01/2015

ISSN (print): 1357-2725

ISSN (electronic): 1878-5875

Publisher: Pergamon Press


DOI: 10.1016/j.biocel.2015.01.025


Altmetrics provided by Altmetric


Funder referenceFunder name
Medical Research Council (MRC) Centre for Neuromuscular Diseases Biobank Newcastle
Medical Research Council (MRC) Centre for the EuroBioBank
309548European Research Council
317433Mitochondrial European Educational Training (MEET), ITN MARIE CURIE PEOPLE
G1000848Medical Research Council (UK)