دورية أكاديمية
أعرض في EDS

Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice.

التفاصيل البيبلوغرافية
العنوان: Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice.
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.
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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
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-23595-x