Abstract
It has long been considered that mitochondrial DNA disease is a rare genetic disorder causing neuromyopathy. However, alterations of mitochondrial DNA recently have been recognized to play an important role in the pathogenesis of so-called common diseases such as heart failure, diabetes, and cancer. Although some of these alterations are inherited, more and more attention is being focused on the accumulation of mitochondrial DNA mutations in somatic cells, particularly terminally differentiated cells such as cardiomyocytes and neurons that occurs with age. Mitochondrial DNA is more vulnerable to alteration than nuclear DNA, mainly for two reasons. First, mitochondria are a major source of intracellular reactive oxygen species (ROS). Therefore mitochondrial DNA is under much stronger oxidative stress than is nuclear DNA. Second, mitochondria have a matrix-side negative membrane potential for oxidative phosphorylation. This membrane potential concentrates lipophilic cations inside mitochondria up to ~1,000-fold. Unfortunately, some therapeutic reagents are lipophilic cations, and such exogenously added chemicals are prone to damage mitochondria. AZT, an anti-HIV drug, causes mitochondrial myopathy as a side effect, which is a typical example of how chemotherapeutics adversely affect metabolism of mitochondrial DNA. In this review, we focus on ROS and chemical damage of mitochondrial DNA in common diseases.
Keywords: mitochondria, mitochondrial dna, reactive oxygen species, oxidative stress, aging, dna damage, dna repair
Current Medicinal Chemistry
Title: Alterations of Mitochondrial DNA in Common Diseases and Disease States: Aging, Neurodegeneration, Heart Failure, Diabetes and Cancer
Volume: 12 Issue: 4
Author(s): Dongchon Kang and Naotaka Hamasaki
Affiliation:
Keywords: mitochondria, mitochondrial dna, reactive oxygen species, oxidative stress, aging, dna damage, dna repair
Abstract: It has long been considered that mitochondrial DNA disease is a rare genetic disorder causing neuromyopathy. However, alterations of mitochondrial DNA recently have been recognized to play an important role in the pathogenesis of so-called common diseases such as heart failure, diabetes, and cancer. Although some of these alterations are inherited, more and more attention is being focused on the accumulation of mitochondrial DNA mutations in somatic cells, particularly terminally differentiated cells such as cardiomyocytes and neurons that occurs with age. Mitochondrial DNA is more vulnerable to alteration than nuclear DNA, mainly for two reasons. First, mitochondria are a major source of intracellular reactive oxygen species (ROS). Therefore mitochondrial DNA is under much stronger oxidative stress than is nuclear DNA. Second, mitochondria have a matrix-side negative membrane potential for oxidative phosphorylation. This membrane potential concentrates lipophilic cations inside mitochondria up to ~1,000-fold. Unfortunately, some therapeutic reagents are lipophilic cations, and such exogenously added chemicals are prone to damage mitochondria. AZT, an anti-HIV drug, causes mitochondrial myopathy as a side effect, which is a typical example of how chemotherapeutics adversely affect metabolism of mitochondrial DNA. In this review, we focus on ROS and chemical damage of mitochondrial DNA in common diseases.
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Cite this article as:
Kang Dongchon and Hamasaki Naotaka, Alterations of Mitochondrial DNA in Common Diseases and Disease States: Aging, Neurodegeneration, Heart Failure, Diabetes and Cancer, Current Medicinal Chemistry 2005; 12 (4) . https://dx.doi.org/10.2174/0929867053363081
DOI https://dx.doi.org/10.2174/0929867053363081 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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