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AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway.

التفاصيل البيبلوغرافية
العنوان: AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway.
المؤلفون: Mak HY; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia., Ouyang Q; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, 210061, Nanjing, China., Tumanov S; Heart Research Institute, The University of Sydney, Newtown, NSW, 2042, Australia.; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia., Xu J; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China., Rong P; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, 210061, Nanjing, China., Dong F; Department of Biology, Southern University of Science and Technology, 518055, Shenzhen, Guangdong, China., Lam SM; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China.; Lipidall Technologies Company Limited, 213022, Changzhou, Jiangsu Province, China., Wang X; Laboratory of Lipid Metabolism, Hebei Medical University, 050017, Shijiazhuang, Hebei, China., Lukmantara I; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia., Du X; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia., Gao M; Laboratory of Lipid Metabolism, Hebei Medical University, 050017, Shijiazhuang, Hebei, China., Brown AJ; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia., Gong X; Department of Biology, Southern University of Science and Technology, 518055, Shenzhen, Guangdong, China., Shui G; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China., Stocker R; Heart Research Institute, The University of Sydney, Newtown, NSW, 2042, Australia.; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia.; School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, 2006, Australia., Huang X; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101, Beijing, China., Chen S; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, 210061, Nanjing, China., Yang H; School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia. h.rob.yang@unsw.edu.au.
المصدر: Nature communications [Nat Commun] 2021 Nov 25; Vol. 12 (1), pp. 6877. Date of Electronic Publication: 2021 Nov 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Acyltransferases/*metabolism , Cytidine Diphosphate Diglycerides/*metabolism , Diacylglycerol Cholinephosphotransferase/*metabolism , Fatty Acids/*metabolism, Acyltransferases/deficiency ; Animals ; Biosynthetic Pathways ; Cell Line ; Diacylglycerol Cholinephosphotransferase/deficiency ; Humans ; Lipid Droplets/metabolism ; Lipogenesis ; Liver/metabolism ; Mice ; Multienzyme Complexes ; Oleic Acid/metabolism ; Phosphatidic Acids/metabolism
مستخلص: AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the glycerol-3-phosphate pathway for the synthesis of phospholipids and triacylglycerols. AGPAT2 is the only AGPAT isoform whose loss-of-function mutations cause a severe form of human congenital generalized lipodystrophy. Paradoxically, AGPAT2 deficiency is known to dramatically increase the level of its product, PA. Here, we find that AGPAT2 deficiency impairs the biogenesis and growth of lipid droplets. We show that AGPAT2 deficiency compromises the stability of CDP-diacylglycerol (DAG) synthases (CDSs) and decreases CDS activity in both cell lines and mouse liver. Moreover, AGPAT2 and CDS1/2 can directly interact and form functional complexes, which promote the metabolism of PA along the CDP-DAG pathway of phospholipid synthesis. Our results provide key insights into the regulation of metabolic flux during lipid synthesis and suggest substrate channelling at a major branch point of the glycerol-3-phosphate pathway.
(© 2021. The Author(s).)
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المشرفين على المادة: 0 (Cytidine Diphosphate Diglycerides)
0 (Fatty Acids)
0 (Multienzyme Complexes)
0 (Phosphatidic Acids)
2UMI9U37CP (Oleic Acid)
EC 2.3.- (Acyltransferases)
EC 2.3.1.52 (2-acylglycerophosphate acyltransferase)
EC 2.7.8.2 (Diacylglycerol Cholinephosphotransferase)
تواريخ الأحداث: Date Created: 20211126 Date Completed: 20211230 Latest Revision: 20221027
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8616899
DOI: 10.1038/s41467-021-27279-4
PMID: 34824276
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-27279-4