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The Consequences of Damaged Mitochondrial DNA

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Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease

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Abstract

The highly conserved mitochondrial DNA (mtDNA) is particularly susceptible to mutations due to its close proximity to respiratory chain, inheritance at birth, lack of histones in structure, as well as ineffective repair mechanisms. Oxidative stress-induced mtDNA damage and mutations are most profound since the mitochondria are constantly exposed to reactive oxygen species generated by electron transport chain. Dysfunctional mitochondria which are commonly observed in aging or diseases, can exacerbate oxidative stress thereby contributing to disease development. MtDNA encompasses essential genes that encode ribosomal RNAs, transfer RNAs, and several respiratory protein complexes. Thus, mutation in mtDNA impairs mitochondrial functions and results in cellular alterations such as disrupted protein synthesis and decreased ATP bioenergetics. The accumulation of mutated mtDNA throughout lifetime and the subsequent mitochondrial dysfunction are implicated in neurodegeneration and multiple mtDNA-related diseases including myoclonic epilepsy with ragged red fibers (MERRF), Leigh syndrome (LS), and Leber’s hereditary optic neuropathy (LHON). Although the management of these mitochondrial diseases remains challenging, the prevention of maternal transmission of mtDNA mutations can be an essential approach. Despite the negative effects caused by mtDNA damage, high mtDNA mutation rates contribute to the genetic polymorphism in the population, which is likely related to human evolution and migration. In this chapter, we will focus on discussing the structure and function of mtDNA, potential sources leading to mtDNA defect, common mtDNA-related diseases, as well as potential treatment for mtDNA damage.

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Acknowledgments

We thank Alexander Ziegler for his assistance during the manuscript preparation.

Conflict of Interest 

The authors declared no conflict of interest.

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Authors and Affiliations

  1. Radiologic Sciences and Respiratory Therapy Division, School of Health and Rehabilitation Sciences, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA

    Li Zuo Ph.D., F.A.C.S.M., Tingyang Zhou B.S. & Chia-Chen Chuang B.S.

  2. Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH, 43210, USA

    Li Zuo Ph.D., F.A.C.S.M., Tingyang Zhou B.S. & Chia-Chen Chuang B.S.

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  1. Li Zuo Ph.D., F.A.C.S.M.
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  2. Tingyang Zhou B.S.
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Correspondence to Li Zuo Ph.D., F.A.C.S.M. .

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  1. College of Health Sciences, Midwestern University, Glendale, Arizona, USA

    Lori M. Buhlman

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Zuo, L., Zhou, T., Chuang, CC. (2016). The Consequences of Damaged Mitochondrial DNA. In: Buhlman, L. (eds) Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-42139-1_3

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