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Potential Mechanisms of Mitochondrial DNA Mediated Acquired Mitochondrial Disease

  • Afshan N. MalikEmail author
  • Hannah S. Rosa
Chapter
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Abstract

Mitochondria are cellular organelles which contain mitochondrial DNA (MtDNA) in the form of an extranuclear genome. MtDNA can be present in 100s to thousands to copies per cell in the body depending on the bioenergetic requirements of the host cell. MtDNA encodes subunits of the electron transport chain and therefore is required to produce cellular energy in the form of ATP. However, MtDNA can also act as an inflammatory molecule since it resembles bacterial DNA, resulting in activation of pathways leading to enhanced cytokine production and chronic inflammation. In the current chapter, we suggest that MtDNA mediated mechanisms that cause systemic mitochondrial dysfunction are involved in many common diseases not traditionally recognised as mitochondrial disease, and we suggest that such disorders could be considered as “acquired mitochondrial diseases”, distinct from primary and secondary mitochondrial disease. Acquired mitochondrial diseases include cardiovascular and neurodegenerative disease as well as diabetic complications, and are associated with oxidative stress and sterile/chronic inflammation in their pathophysiology. We propose a mechanism of how systemic damage to MtDNA, mediated through oxidative stress, can cause inflammation and bioenergetic deficit. Some recent evidence of the proposed mechanism is provided for diabetic nephropathy, a complication of diabetes, which has not traditionally been regarded as a disease of mitochondrial dysfunction. According to the hypothesis proposed, it may be possible to use MtDNA levels in body fluids or cells to predict risk of acquired diseases of mitochondrial dysfunction, and to design novel therapies targeting the specific MtDNA mediated pathways.

Keywords

Mitochondrial DNA Mitochondrial dysfunction Acquired disease Metabolism Biomarker MtDNA Acquired mitochondrial disease Inflammation Oxidative stress 
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Notes

Acknowledgements

Thanks to Dr. Anna Czajka for donating Fig. 4. HSR is supported by an EFSD grant.

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Diabetes Research Group, Faculty of Life Sciences and MedicineKing’s College LondonLondonUK

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