Abstract
Human complex I (NADH:ubiquinone oxidoreductase; EC 1.6.5.3) is the first and largest multi-protein assembly of the mitochondrial oxidative phosphorylation (OXPHOS) system; the final biochemical cascade of events leading to the production of ATP. The complex consists of 46 subunits, 7 encoded by the mitochondrial DNA and the remainder by the nuclear genome. In recent years, numerous gene mutations leading to an isolated complex I deficiency have been characterized in both genomes. Disorders associated with complex I deficiency (OMIM 252010) mostly lead to multi-system disorders affecting brain, skeletal muscle and the heart. Of these, Leigh syndrome, a progressive fatal encephalopathy symmetrically affecting specific areas of the brain, brainstem and myelin, is the most frequently observed phenotype. Here, we review the current understanding of the cell biological consequences of isolated complex I deficiencies and propose further directions the field needs to take in order to develop rational treatment strategies for these devastating disorders.
Keywords: mitochondria, cell biology, oxidative phosphorylation, leigh disease, complex I, mitochondrial medicine
Current Neurovascular Research
Title: Cell Biological Consequences of Mitochondrial NADH: Ubiquinone Oxidoreductase Deficiency
Volume: 1 Issue: 1
Author(s): Jan A.M. Smeitink, Lambert W.P.J. van den Heuvel, Werner J.H. Koopman, Leo G.J. Nijtmans, Cristina Ugalde and Peter H.G.M. Willems
Affiliation:
Keywords: mitochondria, cell biology, oxidative phosphorylation, leigh disease, complex I, mitochondrial medicine
Abstract: Human complex I (NADH:ubiquinone oxidoreductase; EC 1.6.5.3) is the first and largest multi-protein assembly of the mitochondrial oxidative phosphorylation (OXPHOS) system; the final biochemical cascade of events leading to the production of ATP. The complex consists of 46 subunits, 7 encoded by the mitochondrial DNA and the remainder by the nuclear genome. In recent years, numerous gene mutations leading to an isolated complex I deficiency have been characterized in both genomes. Disorders associated with complex I deficiency (OMIM 252010) mostly lead to multi-system disorders affecting brain, skeletal muscle and the heart. Of these, Leigh syndrome, a progressive fatal encephalopathy symmetrically affecting specific areas of the brain, brainstem and myelin, is the most frequently observed phenotype. Here, we review the current understanding of the cell biological consequences of isolated complex I deficiencies and propose further directions the field needs to take in order to develop rational treatment strategies for these devastating disorders.
Export Options
About this article
Cite this article as:
Smeitink A.M. Jan, van den Heuvel W.P.J. Lambert, Koopman J.H. Werner, Nijtmans G.J. Leo, Ugalde Cristina and Willems H.G.M. Peter, Cell Biological Consequences of Mitochondrial NADH: Ubiquinone Oxidoreductase Deficiency, Current Neurovascular Research 2004; 1 (1) . https://dx.doi.org/10.2174/1567202043480224
DOI https://dx.doi.org/10.2174/1567202043480224 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- 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
Related Articles
-
Tissue Doppler Imaging: Beautiful Noise
Current Cardiology Reviews Curcumin: A Natural Product for Diabetes and its Complications
Current Topics in Medicinal Chemistry p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets Regulation of Self-Reactive T Cells by Human Immunoglobulins- Implications for Multiple Sclerosis Therapy
Current Pharmaceutical Design How Cardiomyocytes Make the Heart Old
Current Pharmaceutical Biotechnology Editorial [Hot Topic: Vascular Complications of Diabetes (Executive Editor: Olga I. Stenina)]
Current Pharmaceutical Design Protectors of the Mitochondrial Permeability Transition Pore Activated by Iron and Doxorubicin
Current Cancer Drug Targets The Fundamental Role of Stress Echo in Evaluating Coronary Artery Disease in Specific Patient Populations
Current Vascular Pharmacology Cardiac Gene Therapy: Therapeutic Potential and Current Progress
Current Gene Therapy Target-based Anti-angiogenic Therapy in Breast Cancer
Current Pharmaceutical Design Pharmacogenomic Considerations in the Treatment of the Pediatric Cardiomyopathy Called Barth Syndrome
Recent Patents on Biotechnology Potential Therapeutic Benefits of Sodium-Glucose Cotransporter 2 Inhibitors in the Context of Ischemic Heart Failure: A State-of-the-Art Review
Cardiovascular & Hematological Agents in Medicinal Chemistry Cardioprotective Effects of Natural Products <i>via</i> the Nrf2 Signaling Pathway
Current Vascular Pharmacology Restoration of Cardiomyocyte Function in Streptozotocin-Induced Diabetic Rats after Treatment with Vanadate in a Tea Decoction
Current Pharmaceutical Biotechnology Hypertensive Left Ventricular Hypertrophy Regression: Does It Matter?
Current Hypertension Reviews Blockade of Apoptosis by ACE Inhibitors and Angiotensin Receptor Antagonists
Current Pharmaceutical Design Contextualizing Genetics for Regional Heart Failure Care
Current Cardiology Reviews Autonomic Nervous System in Viral Myocarditis: Pathophysiology and Therapy
Current Pharmaceutical Design Targeting Prenylated RAS Modifying Enzymes in Cancer Cells
Current Signal Transduction Therapy Emerging Role for Antioxidant Therapy in Protection Against Diabetic Cardiac Complications: Experimental and Clinical Evidence for Utilization of Classic and New Antioxidants
Current Cardiology Reviews