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Identification of cytochrome b5 CYTB-5.1 and CYTB-5.2 in C. elegans; evidence for differential regulation of SCD.

Biochim. Biophys. Acta. 2018 Mar;1863(3):235-246. Epub 2017 Dec 10
Baoshen He 1 , Jingjing Zhang 2 , Yanli Wang 3 , Yamei Li 4 , Xiaoju Zou 5 , Bin Liang 6
Baoshen He 1 , Jingjing Zhang 2 , Yanli Wang 3 , Yamei Li 4 , Xiaoju Zou 5 , Bin Liang 6
+ et al

[No authors listed]

Author information
  • 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
  • 2 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; Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
  • 3 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.
  • 4 School of Life Sciences, University of Science and Technology of China, Hefei 230036, China.
  • 5 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.
  • 6 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; Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China. Electronic address: liangb@mail.kiz.ac.cn.

摘要


Unsaturated fatty acids (UFAs) play crucial roles in living organisms regarding development, energy metabolism, stress resistance, etc. The biosynthesis of UFAs starts from the introduction of the first double bond by stearoyl-CoA desaturase (SCD), converting saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs). This desaturation is considered to be an aerobic process that requires cytochrome b5 reductase, cytochrome b5 and SCD. However, this enzyme system remains elusive in Caenorhabditis elegans. Here, we show that inactivation by knockdown or mutation (gk442189) of putative cytochrome b5 genes cytb-5.1 led to reduced conversion of C18:0 to C18:1(n-9) by SCD desaturases FAT-6/7 in C. elegans. On the contrary, and cytb-5.2(gk113588) mutant worms showed decreased conversion of C16:0 to C16:1(n-7) by FAT-5 desaturase. Dietary supplementation with C18:1(n-9) and C18:2(n-6) also showed that CYTB-5.1 is likely required for the activity of FAT-6/7 desaturases, but not for FAT-1 to FAT-4 desaturases. Interestingly, co-immunoprecipitation (Co-IP) demonstrated that either FAT-7 or FAT-5 has ability to interact with both CYTB-5.1 and CYTB-5.2. Moreover, duanyu1615 knockdown of cytb-5.1 upregulates the transcriptional and translational expression of fat-5 to fat-7, which may be due to the feedback induction by reduced C18:1(n-9) and downstream fatty acids. Furthermore, both CYTB-5.1 and CYTB-5.2 are involved in fat accumulation, fertility and lifespan in worms, which may be independent of changes in fatty acid compositions. Collectively, these findings for the first time reveal the differential regulation of various SCDs by distinct cytochrome b5 CYTB-5.1 and CYTB-5.2 in the biosynthesis of UFAs in C. elegans.

KEYWORDS: Caenorhabditis elegans, Cytochrome b5, Stearoyl-CoA desaturase (SCD), Unsaturated fatty acids (UFAs)