The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans |
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| Institution: | 1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;2. Department of Life Science and Biotechnology, Key Laboratory of Special Biological Resource Development and Utilization of University in Yunnan Province, Kunming University, Kunming 650214, China;3. College of Fisheries, Henan Normal University, Xinxiang, Henan 453007, China;4. Key Laboratory of Puer Tea Science, Ministry of Education (Yunnan Agricultural University), Kunming 650201, China;5. Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou 215006, China;6. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China;1. Department of Cardiology, Beijing Hospital, Beijing 100730, China;2. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China;3. Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China;4. Department of Cardiology, Fuwai Hospital, Beijing 100037, China;5. Department of Clinical Chemistry, Beijing Hospital, Beijing 100730, China;1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;2. Yuxi City Center for Disease Control and Prevention, Yuxi, Yunnan 653100, China;3. Wenshan Institute of Dermatology, Wenshan, Yunnan 663000, China;4. Department of Dermatology, the First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, 650032, China;5. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650201, China |
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| Abstract: | Polyunsaturated fatty acids (PUFAs) are fatty acids with backbones containing more than one double bond, which are introduced by a series of desaturases that insert double bonds at specific carbon atoms in the fatty acid chain. It has been established that desaturases need flavoprotein-NADH-dependent cytochrome b5 reductase (simplified as cytochrome b5 reductase) and cytochrome b5 to pass through electrons for activation. However, it has remained unclear how this multi-enzyme system works for distinct desaturases. The model organism Caenorhabditis elegans contains seven desaturases (FAT-1, -2, -3, -4, -5, -6, -7) for the biosynthesis of PUFAS, providing an excellent model in which to characterize different desaturation reactions. Here, we show that RNAi inactivation of predicted cytochrome b5 reductases hpo-19 and T05H4.4 led to increased levels of C18:1n − 9 but decreased levels of PUFAs, small lipid droplets, decreased fat accumulation, reduced brood size and impaired development. Dietary supplementation with different fatty acids showed that HPO-19 and T05H4.4 likely affect the activity of FAT-1, FAT-2, FAT-3, and FAT-4 desaturases, suggesting that these four desaturases use the same cytochrome b5 reductase to function. Collectively, these findings indicate that cytochrome b5 reductase HPO-19/T05H4.4 is required for desaturation to biosynthesize PUFAs in C. elegans. |
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