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.
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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 |
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