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The genetics and pathology of mitochondrial disease

Lookup NU author(s): Dr Charlotte Alston, Dr Mariana Rocha, Dr Nichola Lax, Emeritus Professor Doug Turnbull, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Mitochondria are double-membrane-bound organelles that are present in all nucleated eukaryotic cells and are responsible for the production of cellular energy in the form of ATP. Mitochondrial function is under dual genetic control-the 16.6-kb mitochondrial genome, with only 37 genes, and the nuclear genome, which encodes the remaining similar to 1300 proteins of the mitoproteome. Mitochondrial dysfunction can arise because of defects in either mitochondrial DNA or nuclear mitochondrial genes, and can present in childhood or adulthood in association with vast clinical heterogeneity, with symptoms affecting a single organ or tissue, or multisystem involvement. There is no cure for mitochondrial disease for the vast majority of mitochondrial disease patients, and a genetic diagnosis is therefore crucial for genetic counselling and recurrence risk calculation, and can impact on the clinical management of affected patients. Next-generation sequencing strategies are proving pivotal in the discovery of new disease genes and the diagnosis of clinically affected patients; mutations in > 250 genes have now been shown to cause mitochondrial disease, and the biochemical, histochemical, immunocytochemical and neuropathological characterization of these patients has led to improved diagnostic testing strategies and novel diagnostic techniques. This review focuses on the current genetic landscape associated with mitochondrial disease, before focusing on advances in studying associated mitochondrial pathology in two, clinically relevant organs-skeletal muscle and brain. (C) 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Publication metadata

Author(s): Alston CL, Rocha MC, Lax NZ, Turnbull DM, Taylor RW

Publication type: Article

Publication status: Published

Journal: Journal of Pathology

Year: 2017

Volume: 241

Issue: 2

Pages: 236-250

Print publication date: 01/01/2017

Online publication date: 23/09/2016

Acceptance date: 16/09/2016

Date deposited: 09/03/2017

ISSN (print): 0022-3417

ISSN (electronic): 1096-9896

Publisher: Wiley-Blackwell Publishing, Inc.


DOI: 10.1002/path.4809


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Funder referenceFunder name
Lily Foundation
UK National Health Service Highly Specialised 'Rare Mitochondrial Disorders of Adults and Children' service
UK NIHR Biomedical Research Centre in Age and Age Related Diseases award
MRC/ESPRC Newcastle Molecular Pathology Node
096919/Z/11/ZWellcome Trust Strategic Award
G016354/1Newcastle University Centre for Ageing and Vitality [Biotechnology and Biological Sciences Research Council]
G016354/1Newcastle University Centre for Ageing and Vitality [Medical Research Council]
G0601943MRC Centre for Neuromuscular Diseases
NIHR-HCS-D12-03-04National Institute for Health Research (NIHR) doctoral fellowship