title: The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans.
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.
authors.affiliation: 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; College of Fisheries, Henan Normal University, Xinxiang, Henan 453007, China.
authors.forename: Yuru
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Linqiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Puer Tea Science, Ministry of Education (Yunnan Agricultural University), Kunming 650201, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou 215006, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Biochemistry and Molecular Biology, Soochow University Medical College, Suzhou 215006, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: 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. Electronic address: xiaojuzou@163.com.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zou
authors.affiliation: 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. Electronic address: liangb@mail.kiz.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D042966:Cytochrome-B(5) Reductase / Q000235:genetics / Q000378:metabolism*; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D066292:Lipid Droplets / Q000378:metabolism; D012098:Reproduction; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases; D042966:Cytochrome-B(5) Reductase
keywords: C. elegans; Cytochrome b5 reductase HPO-19 and T05H4.4; Fatty acid desaturation; Polyunsaturated fatty acids (PUFAs)