دورية أكاديمية
Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice.
العنوان: | Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice. |
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المؤلفون: | Li Y; Division of General Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Imai N; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Nicholls HT; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Roberts BR; Department of Biochemistry, Emory University, Atlanta, GA, USA., Goyal S; Division of General Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Krisko TI; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA., Ang LH; Division of General Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Tillman MC; Department of Biochemistry, Emory University, Atlanta, GA, USA., Roberts AM; Department of Biochemistry, Emory University, Atlanta, GA, USA., Baqai M; Division of General Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Ortlund EA; Department of Biochemistry, Emory University, Atlanta, GA, USA., Cohen DE; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA. dcohen@med.cornell.edu., Hagen SJ; Division of General Surgery, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA. shagen@bidmc.harvard.edu.; Department of Surgery, Harvard Medical School, Boston, MA, USA. shagen@bidmc.harvard.edu. |
المصدر: | Nature communications [Nat Commun] 2021 Jun 09; Vol. 12 (1), pp. 3493. Date of Electronic Publication: 2021 Jun 09. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; 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: | Energy Metabolism*/drug effects, Palmitoyl-CoA Hydrolase/*metabolism, Adipose Tissue, Brown/metabolism ; Adrenergic Agonists/pharmacology ; Amino Acid Sequence ; Animals ; Fatty Acids/metabolism ; Intracellular Space/metabolism ; Lipid Droplets/metabolism ; Mice ; Mitochondria/metabolism ; Oxidation-Reduction ; Palmitoyl-CoA Hydrolase/chemistry ; Palmitoyl-CoA Hydrolase/genetics ; Phosphorylation/drug effects ; Protein Aggregates ; Serine/metabolism ; Thermogenesis/drug effects |
مستخلص: | In brown adipose tissue, thermogenesis is suppressed by thioesterase superfamily member 1 (Them1), a long chain fatty acyl-CoA thioesterase. Them1 is highly upregulated by cold ambient temperature, where it reduces fatty acid availability and limits thermogenesis. Here, we show that Them1 regulates metabolism by undergoing conformational changes in response to β-adrenergic stimulation that alter Them1 intracellular distribution. Them1 forms metabolically active puncta near lipid droplets and mitochondria. Upon stimulation, Them1 is phosphorylated at the N-terminus, inhibiting puncta formation and activity and resulting in a diffuse intracellular localization. We show by correlative light and electron microscopy that Them1 puncta are biomolecular condensates that are inhibited by phosphorylation. Thus, Them1 forms intracellular biomolecular condensates that limit fatty acid oxidation and suppress thermogenesis. During a period of energy demand, the condensates are disrupted by phosphorylation to allow for maximal thermogenesis. The stimulus-coupled reorganization of Them1 provides fine-tuning of thermogenesis and energy expenditure. |
References: | Biochemistry. 2018 May 1;57(17):2478-2487. (PMID: 29517898) Nucleic Acids Res. 2018 Jul 2;46(W1):W329-W337. (PMID: 29860432) J Biol Chem. 2012 Nov 30;287(49):41446-57. (PMID: 23066022) Am J Physiol Gastrointest Liver Physiol. 2017 Jul 1;313(1):G50-G61. (PMID: 28385694) Microsc Microanal. 2014 Feb;20(1):152-63. (PMID: 24252586) J Biol Chem. 2008 Jan 4;283(1):231-236. (PMID: 17962198) Nucleic Acids Res. 2010 Jan;38(Database issue):D161-6. (PMID: 19858104) Traffic. 2019 Sep;20(9):623-638. (PMID: 31152627) Nat Commun. 2018 Dec 3;9(1):5128. (PMID: 30510204) J Lipid Res. 2012 Dec;53(12):2620-31. (PMID: 22993230) Trends Endocrinol Metab. 2017 Jul;28(7):473-484. (PMID: 28385385) Hepatology. 2019 Aug;70(2):496-510. (PMID: 30516845) Nature. 2012 Mar 07;483(7389):336-40. (PMID: 22398450) Elife. 2018 Feb 09;7:. (PMID: 29424691) Gastroenterology. 2011 Dec;141(6):2064-75. (PMID: 21925124) Cell Metab. 2018 Apr 3;27(4):869-885.e6. (PMID: 29617645) Bioinformatics. 2014 Sep 1;30(17):2501-2. (PMID: 24825614) PLoS Comput Biol. 2009 May;5(5):e1000376. (PMID: 19412530) Lipids. 2010 Jun;45(6):479-89. (PMID: 20509000) Cell Metab. 2006 May;3(5):333-41. (PMID: 16679291) J Cell Biol. 1970 Aug;46(2):252-66. (PMID: 4194652) Nucleic Acids Res. 2018 Jan 4;46(D1):D493-D496. (PMID: 29040681) J Biol Chem. 2015 Jun 12;290(24):15112-20. (PMID: 25918168) Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. (PMID: 30395287) Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5417-22. (PMID: 22427358) Physiol Rev. 2004 Jan;84(1):277-359. (PMID: 14715917) J Lipid Res. 2007 Dec;48(12):2547-59. (PMID: 17878492) Mol Metab. 2016 Feb 23;5(5):340-351. (PMID: 27110486) Cell. 2019 Jan 24;176(3):419-434. (PMID: 30682370) Dev Cell. 2015 Mar 23;32(6):678-92. (PMID: 25752962) Protein Sci. 2018 Jan;27(1):331-340. (PMID: 29076577) Mol Cell. 2016 Jul 7;63(1):72-85. (PMID: 27392146) J Proteome Res. 2020 May 1;19(5):2035-2042. (PMID: 32195589) EMBO J. 2017 Oct 16;36(20):2951-2967. (PMID: 28790177) Annu Rev Nutr. 2014;34:1-30. (PMID: 24819326) Biochem J. 2001 Nov 15;360(Pt 1):135-42. (PMID: 11696000) Cell. 2010 Dec 23;143(7):1174-89. (PMID: 21183079) Cell Metab. 2010 Jul 7;12(1):53-64. (PMID: 20620995) Cell. 2012 May 11;149(4):768-79. (PMID: 22579282) J Mol Biol. 2005 Apr 8;347(4):827-39. (PMID: 15769473) |
معلومات مُعتمدة: | T32 GM008602 United States GM NIGMS NIH HHS; S10 OD019988 United States OD NIH HHS; R01 DK056626 United States DK NIDDK NIH HHS; R01 DK103046 United States DK NIDDK NIH HHS; P30 DK034854 United States DK NIDDK NIH HHS; R01 DK048873 United States DK NIDDK NIH HHS; T32 DK007533 United States DK NIDDK NIH HHS |
المشرفين على المادة: | 0 (Adrenergic Agonists) 0 (Fatty Acids) 0 (Protein Aggregates) 452VLY9402 (Serine) EC 3.1.2.- (Thea protein, mouse) EC 3.1.2.2 (Palmitoyl-CoA Hydrolase) |
تواريخ الأحداث: | Date Created: 20210610 Date Completed: 20210622 Latest Revision: 20230120 |
رمز التحديث: | 20230120 |
مُعرف محوري في PubMed: | PMC8190112 |
DOI: | 10.1038/s41467-021-23595-x |
PMID: | 34108467 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-021-23595-x |