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: ジャーナルへの寄稿評論記事

95 引用 (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.

元の言語英語
ページ(範囲)429-441
ページ数13
ジャーナルCurrent Medicinal Chemistry
12
発行部数4
DOI
出版物ステータス出版済み - 1 1 2005

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Heart Neoplasms
Medical problems
Mitochondrial DNA
Heart Failure
Aging of materials
Mitochondria
Membrane Potentials
Cations
Reactive Oxygen Species
Mitochondrial Myopathies
Membranes
Anti-HIV Agents
Mitochondrial Diseases
Inborn Genetic Diseases
Oxidative stress
DNA
Oxidative Phosphorylation
Cardiac Myocytes
Metabolism
Neurons

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

これを引用

Alterations of mitochondrial DNA in common diseases and disease states : Aging, neurodegeneration, heart failure, diabetes and cancer. / Kang, Dongchon; Hamasaki, Naotaka.

:: Current Medicinal Chemistry, 巻 12, 番号 4, 01.01.2005, p. 429-441.

研究成果: ジャーナルへの寄稿評論記事

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