Journal of Inherited Metabolic Disease

, Volume 34, Issue 2, pp 309–313

Altering the balance between healthy and mutated mitochondrial DNA

Mitochondrial Medicine

DOI: 10.1007/s10545-010-9122-6

Cite this article as:
Smith, P.M. & Lightowlers, R.N. J Inherit Metab Dis (2011) 34: 309. doi:10.1007/s10545-010-9122-6

Abstract

Pathogenic mutations of the mitochondrial genome are frequently found to co-exist with wild-type mtDNA molecules, a state known as heteroplasmy. In most disease cases, the mutation is recessive with manifestation of a clinical phenotype occurring when the proportion of mutated mtDNA exceeds a high threshold. The concept of increasing the ratio of healthy to mutated mtDNA as a means to correcting the biochemical defect has received much attention. A number of strategies are highlighted in this article, including manipulation of the mitochondrial genome by antigenomic drugs or restriction endonucleases, zinc finger peptide-targeted nucleases and exercise-induced gene shifting. The feasibility of these approaches has been demonstrated in a number of models, however more work is necessary before use in human patients.

Abbreviations

ATP

Adenosine 5′-triphosphate

LHON

Leber hereditary optic neuropathy

MERRF

Myoclonic epilepsy with ragged red fibres

mtDNA

Mitochondrial DNA

NARP

Neurogenic muscle weakness ataxia and retinitis

OXPHOS

Oxidative phosphorylation

PNAs

Peptide nucleic acids

ZPFs

Zinc finger peptides

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  1. 1.Mitochondrial Research Group, Institute of Ageing and HealthMedical SchoolNewcastle upon TyneUK