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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Prokinetic Agents and QT Prolongation: A Familiar Scene with New Actors
Current Drug Safety Insights into Immunophilin Structure and Function
Current Medicinal Chemistry Therapeutic Approaches for Reducing C-Reactive Protein (CRP) Levels and the Associated Cardiovascular Risk
Current Chemical Biology The Chick Embryo Chorioallantoic Membrane as a Model for in vivo Research on Anti-Angiogenesis
Current Pharmaceutical Biotechnology Recent Advances in Sepsis Research: Novel Biomarkers and Therapeutic Targets
Current Medicinal Chemistry Emerging Concepts on Inhibitors of Indoleamine 2,3-Dioxygenase in Rheumatic Diseases
Current Medicinal Chemistry B-Type Natriuretic Peptide for Diagnosis and Therapy
Recent Patents on Cardiovascular Drug Discovery Endothelial Dysfunction and Coronary Atherosclerosis
Current Drug Targets - Cardiovascular & Hematological Disorders The Role of PPARs in Pathological Cardiac Hypertrophy and Heart Failure
Current Pharmaceutical Design Atypical Takotsubo Cardiomyopathy with Hypokinetic Left Mid-ventricle and Apical Wall Sparing: A Case Report and Literature Review
Current Cardiology Reviews Cellular Therapy for Myocardial Repair
Current Cardiology Reviews Collagen Cross-link Breakers:A Beginning of a New Era in the Treatment of Cardiovascular Changes Associated with Aging,Diabetes,and Hypertension
Current Drug Targets - Cardiovascular & Hematological Disorders The Future of Angiotensin II Inhibition in Cardiovascular Medicine
Current Drug Targets - Cardiovascular & Hematological Disorders Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect
Endocrine, Metabolic & Immune Disorders - Drug Targets Heart Failure Pharmacotherapy: Differences Between Adult and Paediatric Patients
Current Medicinal Chemistry Variability in the Response to Non-pharmacological Treatments in Patients with Cardiovascular Diseases
Current Pharmacogenomics and Personalized Medicine Editorial [Hot Topic Hot Potatoes in AF (Guest Editor: Jane Caldwell)]
Current Cardiology Reviews Hypoxia and Fetal Heart Development
Current Molecular Medicine Recent Advances in Antiarrhythmic Drug Treatment of Atrial Fibrillation
Recent Patents on Cardiovascular Drug Discovery Novel Anti-arrhythmic Medications in the Treatment of Atrial Fibrillation
Current Cardiology Reviews