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 |
![](/images/wayfinder.jpg)
- 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
-
Selective Inhibition of Phosphodiesterases 4A, B, C and D Isoforms in Chronic Respiratory Diseases: Current and Future Evidences
Current Pharmaceutical Design MicroRNAs: A Critical Regulator and a Promising Therapeutic and Diagnostic Molecule for Diabetic Cardiomyopathy
Current Gene Therapy A beta oligomerization A Therapeutic Target for Alzheimers Disease
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Implications of Epigenetic Mechanisms and their Targets in Cerebral Ischemia Models
Current Neuropharmacology Editorial (Thematic Issue: Mechanistic Biomarkers: The Field for the Development of Non-Pharmaceutical and Pharmaceutical Approaches to Diagnostics, Prevention and Treatment of Chronic Diseases)
Current Pharmaceutical Design Role of Coronary Microvascular Endothelial Dysfunction in the Development of Heart Failure
Current Cardiology Reviews Pharmacological Therapy of Pericardial Diseases
Current Pharmaceutical Design Discovery and Development of Topoisomerase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Persistent Pulmonary Hypertension of the Newborn: Physiology, Hemodynamic Assessment and Novel Therapies
Current Pediatric Reviews Non-Analgesic Effects of Opioids: Cardiovascular Effects of Opioids and their Receptor Systems
Current Pharmaceutical Design COVID-19 Effects on Geriatric Population and Failures of Aminoquinoline Therapy: Compilation of Studies from EU, USA, and China; Safety and Efficacy of Vaccines in the Prevention and Treatment of COVID-19
Current Medicinal Chemistry The Role of Transforming Growth Factor-β in Cardiac Fibrosis
Current Enzyme Inhibition Chromium-Picolinate Therapy in Diabetes Care: Individual Outcomes Require New Guidelines and Navigation by Predictive Diagnostics
Infectious Disorders - Drug Targets Cardioprotective Effects of Indian Gooseberry (Emblica officinalis Gaertn) and its Phytochemicals: A Review
Current Nutrition & Food Science Cord Blood as Diagnostic Window for Preeclampsia
Recent Patents on Biomarkers Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Endocrine, Metabolic & Immune Disorders - Drug Targets Ferroptotic Cell Death: New Regulatory Mechanisms for Metabolic Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Heat Shock Protein-60 and Risk for Cardiovascular Disease
Current Pharmaceutical Design Strain and Strain Rate Imaging by Echocardiography - Basic Concepts and Clinical Applicability
Current Cardiology Reviews Disease-Specific iPS Cell Models in Neuroscience
Current Molecular Medicine