The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans

Zhang, Yuru; Wang, Haizhen; Zhang, Jingjing; Hu, Ying; Zhang, Linqiang; Wu, Xiaoyun; Su, Xiong; Li, Tingting; Zou, Xiaoju; Liang, Bin

doi:10.1016/j.bbalip.2016.01.009

Cited by 19 publications

(12 citation statements)

References 42 publications

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“…This results in the activation of hydrogen at the carbon of incipient double bond in substrate. The product of this relatively slow stage is a very short-lived carbon-centered radical [15,16]. During the second stage, this transient molecule loses the second hydrogen via rapid disproportionation, which leads to the formation of the final product with a new double bond, along with two molecules of water [17].…”

Section: Activity Of Unsaturated Fatty Acid Desaturasesmentioning

confidence: 99%

Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease

Czumaj

Śledziński

2020

Nutrients

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Polyunsaturated fatty acids (PUFAs) are considered one of the most important components of cells that influence normal development and function of many organisms, both eukaryotes and prokaryotes. Unsaturated fatty acid desaturases play a crucial role in the synthesis of PUFAs, inserting additional unsaturated bonds into the acyl chain. The level of expression and activity of different types of desaturases determines profiles of PUFAs. It is well recognized that qualitative and quantitative changes in the PUFA profile, resulting from alterations in the expression and activity of fatty acid desaturases, are associated with many pathological conditions. Understanding of underlying mechanisms of fatty acid desaturase activity and their functional modification will facilitate the development of novel therapeutic strategies in diseases associated with qualitative and quantitative disorders of PUFA.

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Section: Activity Of Unsaturated Fatty Acid Desaturasesmentioning

confidence: 99%

Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease

Czumaj

Śledziński

2020

Nutrients

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“…The desaturation of fatty acids is performed by a multi-enzyme complex comprising cytochrome b5, cytochrome b5 reductase and fatty acid desaturase. FAT-2 carries the putative cytochrome b5 domain but requires the specific cytochrome b5 reductase HPO-19 and T05H4.4 for activation in C. elegans 51 . In D. melanogaster , the putative cytochrome 5b reductase CG5946 (NP_729751.1) has 59% and 55% amino acid sequence identity with HPO-19 (NP_504638.1) and T05H4.4 (NP_504639.1), respectively, and likely donates electrons for FAT-2 activity.…”

Section: Discussionmentioning

confidence: 99%

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila

Suito

Nagao

Takeuchi

et al. 2020

Sci Rep

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polyunsaturated fatty acids (pUfAs) play crucial roles in adaptation to cold environments in a wide variety of animals and plants. However, the mechanisms by which PUFAs affect thermoregulatory behaviour remain elusive. Thus, we investigated the roles of PUFAs in thermoregulatory behaviour of Drosophila melanogaster. To this end, we generated transgenic flies expressing Caenorhabditis elegans Δ12 fatty acid desaturase (FAT-2), which converts mono-unsaturated fatty acids to PUFAs such as linoleic acid [C18:2 (n-6)] and linolenic acid [C18:3 (n-3)]. Neuron-specific expression of FAT-2 using the GAL4/UAS expression system led to increased contents of C18:2 (n-6)-containing phospholipids in central nerve system (CNS) and caused significant decreases in preferred temperature of third instar larvae. In genetic screening and calcium imaging analyses of thermoreceptor-expressing neurons, we demonstrated that ectopic expression of FAT-2 in TRPA1-expressing neurons led to decreases in preferred temperature by modulating neuronal activity. We conclude that functional expression of FAT-2 in a subset of neurons changes the thermoregulatory behaviour of D. melanogaster, likely by modulating quantities of PUFA-containing phospholipids in neuronal cell membranes. Polyunsaturated fatty acids (PUFAs) contain multiple double bonds in their hydrocarbon chains and, as bioactive lipids, regulate various animal physiological functions, such as those relating to immunity, reproduction and energy metabolism 1,2. PUFAs have also been implicated in thermal adaptation, particularly cold adaptation, because the cis double bonds in PUFAs create the "kinks" in hydrocarbon chain structures that reduce the packing of phospholipids, thus increasing membrane fluidity at low temperatures 3,4. For instance, ectothermic fish that live in low temperatures have high PUFA contents in phospholipids 5,6 , facilitating membrane fluidity 7 and modulating the activities of membrane proteins, such as Na +-K + ATPase 8 , in cold environments. Most organisms produce mono-unsaturated fatty acids from saturated fatty acids through the actions of Δ9 fatty acid desaturases 9-13. In mammals, PUFAs such as arachidonic acid [C20:4 (n-6)] and eicosapentaenoic acid [C20:5 (n-3)] are produced from linoleic acid [C18:2 (n-6)] and α-linolenic acid [C18:3 (n-3)], respectively, by Δ5 and Δ6 fatty acid desaturases. In contrast, Δ12 fatty acid desaturases that convert oleic acid [C18:1 (n-9)] to C18:2 (n-6), such as those in nematode Caenorhabditis elegans 14 , American cockroach 15 and cricket 16 , are found in few animals. Therefore, most animals have to obtain PUFAs, such as C18:2 (n-6) and C18:3 (n-3), from their diet. In bacteria 17 , protozoa 18 , algae 19,20 and plants 21,22 , Δ12 fatty acid desaturase can be reportedly induced following exposures to low temperatures. Hence, its biosynthetic product C18:2 (n-6) is thought to play crucial roles in low-temperature acclimation. C. elegans synthesises PUFAs using seven desaturases (FAT-1, FAT-2, FAT-3, FAT-4, FAT-5, FAT-6, ...

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“…They found a strong correlation between the expression of KAS-1 and saturated fatty acid and biomass yield. The KAS-1 gene is known to catalyze the production of 18-carbon fatty acid from 16carbon fatty acid in which palmitic and steric acid are the nal product of the fatty acid synthesis [49].…”

Section: Effect Of Culture Conditions On the Expression Of Rbcl And Accd Genes Of Chlorella Sp T4mentioning

confidence: 99%

Lipid Productivity and Biosynthesis Genes Response of Indigenous Chlorella sp. T4 Strain under Different Nitrogen and Phosphorus Load

Gumbi

Kumar

Olaniran

2021

Preprint

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Microalgae can synthesize and accumulate high neutral lipids upon exposure to abiotic stress such as nutrient starvation or limitation. In this study, indigenous microalgae Chlorella sp. T4 was cultivated in nitrogen and phosphorus under both limiting and replete conditions. Growth, lipid yield, fatty acid profiles and biosynthetic gene expression levels were determined to ascertain cell’s response under these conditions. An impaired cell growth was observed under nitrogen limiting condition, evident by the lowest biomass yield (0.58±0.03 g L−1) as revealed by low quantum efficiency of photosystem II (Fv/Fm) value and chlorophyll a content. An increase in lipid content yield was observed under nitrogen and phosphorus limiting conditions as compared to the control. Nutrient limiting conditions produced fatty acid methyl ester that is suitable for biodiesel production compared to the control (BG-11). Gene expression analysis using real time q-PCR for photosynthesis (rbcL) and lipid biosynthesis (accD, KAS-1, ω-6 FAD, ω-3 FAD) genes revealed different expression levels under both limiting and replete conditions. Under nutrient limiting conditions, increase in the expression of accD, KAS-1, ω-6 FAD and ω-3 FAD genes was observed, whereas a decrease in rbcL gene expression level was noted. A significant correlation could be drawn between the expression levels of the biosynthetic genes and growth rate, biomass yield, physiological response, lipid yield and fatty acid composition. These results provide an insight into the physiological response and gene expression level under different nutrient levels, which could be harnessed for future genetic engineering of Chlorella sp. T4 for improved lipid production.

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The cytochrome b5 reductase HPO-19 is required for biosynthesis of polyunsaturated fatty acids in Caenorhabditis elegans

Cited by 19 publications

References 42 publications

Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease

Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease

Functional expression of Δ12 fatty acid desaturase modulates thermoregulatory behaviour in Drosophila

Lipid Productivity and Biosynthesis Genes Response of Indigenous Chlorella sp. T4 Strain under Different Nitrogen and Phosphorus Load

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