Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research

Paraskevaidi, Maria, Martin-Hirsch, Pierre L., Kyrgiou, Maria and Martin, Francis L orcid iconORCID: 0000-0001-8562-4944 (2016) Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research. Mutagenesis . ISSN 0267-8357

[thumbnail of Author-accepted manuscript]
PDF (Author-accepted manuscript) - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.


Official URL: http://doi.org/10.1093/mutage/gew058


Mitochondrial diseases have been extensively investigated over the last three decades but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases, but is also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell’s functionality. Specifically, we suggest that environmental agents can cause damage by generating abasic sites in mitochondrial DNA, which consequently lead to mutagenesis. Abasic sites are observed in DNA after spontaneous loss of a nucleic base (e.g., “apurinic sites” after loss of purines, adenine or guanine) or through base excision repair; if left unrepaired, they can produce mutagenic DNA lesions. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests towards eliminating these maternally-inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. More effort is needed into further unravelling the relationship between xenobiotics and mitochondria as the extent of influence in mitochondrial pathogenesis is increasingly recognised.

Repository Staff Only: item control page