Alterations of mitochondrial DNA in common diseases and disease states: Aging, neurodegeneration, heart failure, diabetes and cancer

Dongchon Kang, Naotaka Hamasaki

研究成果: Contribution to journalReview article査読

101 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)429-441
ページ数13
ジャーナルCurrent Medicinal Chemistry
12
4
DOI
出版ステータス出版済み - 1 1 2005

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子医療
  • 薬理学
  • 創薬
  • 有機化学

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