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


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.



Adenosine 5′-triphosphate


Leber hereditary optic neuropathy


Myoclonic epilepsy with ragged red fibres


Mitochondrial DNA


Neurogenic muscle weakness ataxia and retinitis


Oxidative phosphorylation


Peptide nucleic acids


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