A Drosophila model of mitochondrial disease caused by a complex I mutation that uncouples proton pumping from electron transfer
| العنوان: | A Drosophila model of mitochondrial disease caused by a complex I mutation that uncouples proton pumping from electron transfer |
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| المؤلفون: | Margaret M. Sedensky, Wichit Suthammarak, Jonathon L. Burman, Leslie S. Itsara, Ernst Bernhard Kayser, Matt Kaeberlein, Adrienne M. Wang, Philip G. Morgan, Leo J. Pallanck |
| المصدر: | Disease Models & Mechanisms, Vol 7, Iss 10, Pp 1165-1174 (2014) Disease Models & Mechanisms |
| بيانات النشر: | The Company of Biologists, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Mitochondrial Diseases, Mitochondrial disease, Protein subunit, Mutant, Neuroscience (miscellaneous), Respiratory chain, Medicine (miscellaneous), lcsh:Medicine, Mitochondrion, medicine.disease_cause, Oxidative Phosphorylation, General Biochemistry, Genetics and Molecular Biology, Electron Transport, 03 medical and health sciences, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), medicine, lcsh:Pathology, Animals, Neurodegeneration, 030304 developmental biology, 0303 health sciences, Mutation, Electron Transport Complex I, biology, lcsh:R, NADH dehydrogenase, Proton Pumps, medicine.disease, Leigh syndrome, Cell biology, Mitochondria, Disease Models, Animal, Biochemistry, biology.protein, Drosophila, Reactive Oxygen Species, 030217 neurology & neurosurgery, Research Article, lcsh:RB1-214 |
| الوصف: | Mutations affecting mitochondrial complex I, a multi-subunit assembly that couples electron transfer to proton pumping, are the most frequent cause of heritable mitochondrial diseases. However, the mechanisms by which complex I dysfunction results in disease remain unclear. Here, we describe a Drosophila model of complex I deficiency caused by a homoplasmic mutation in the mitochondrial-encoded NADH dehydrogenase subunit 2 (ND2) gene. We show that ND2 mutants exhibit phenotypes that resemble symptoms of mitochondrial disease, including shortened lifespan, progressive neurodegeneration, diminished neural mitochondrial membrane potential, and lower levels of neural ATP. Our biochemical studies of ND2 mutants reveal that complex I is unable to efficiently couple electron transfer to proton pumping. Thus, our study provides evidence that the ND2 subunit participates directly in the proton pumping mechanism of complex I. Together, our findings support the model that diminished respiratory chain activity, and consequent energy deficiency, are responsible for the pathogenesis of complex I-associated neurodegeneration. |
| اللغة: | English |
| تدمد: | 1754-8411 1754-8403 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::16fdfa331e68d9522f88e2382ea9e3ef http://dmm.biologists.org/content/7/10/1165 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....16fdfa331e68d9522f88e2382ea9e3ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17548411 17548403 |
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