Adenylate cyclase 10 promotes brown adipose tissue thermogenesis
Summary: Brown adipose tissue (BAT) thermogenesis dissipates energy through heat production and thereby it opposes metabolic disease. It is mediated by mitochondrial membrane uncoupling, yet the mechanisms sustaining the mitochondrial membrane potential (ΔΨm) in brown adipocytes are poorly understoo...
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000938 |
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| author | Anupam Das Christine Mund Eman Hagag Ruben Garcia-Martin Eleftheria Karadima Anke Witt Mirko Peitzsch Andreas Deussen Triantafyllos Chavakis Thomas Noll Vasileia Ismini Alexaki |
| author_facet | Anupam Das Christine Mund Eman Hagag Ruben Garcia-Martin Eleftheria Karadima Anke Witt Mirko Peitzsch Andreas Deussen Triantafyllos Chavakis Thomas Noll Vasileia Ismini Alexaki |
| author_sort | Anupam Das |
| collection | DOAJ |
| description | Summary: Brown adipose tissue (BAT) thermogenesis dissipates energy through heat production and thereby it opposes metabolic disease. It is mediated by mitochondrial membrane uncoupling, yet the mechanisms sustaining the mitochondrial membrane potential (ΔΨm) in brown adipocytes are poorly understood. Here we show that isocitrate dehydrogenase (IDH) activity and the expression of the soluble adenylate cyclase 10 (ADCY10), a CO2/bicarbonate sensor residing in mitochondria, are upregulated in BAT of cold-exposed mice. IDH inhibition or ADCY10 deficiency reduces cold resistance of mice. Mechanistically, IDH increases the ΔΨm in brown adipocytes via ADCY10. ADCY10 sustains complex I activity and the ΔΨm via exchange protein activated by cAMP1 (EPAC1). However, neither IDH nor ADCY10 inhibition affect uncoupling protein 1 (UCP1) expression. Hence, we suggest that ADCY10, acting as a CO2/bicarbonate sensor, mediates the effect of IDH on complex I activity through cAMP-EPAC1 signaling, thereby maintaining the ΔΨm and enabling thermogenesis in brown adipocytes. |
| format | Article |
| id | doaj-art-8184bb6cdf1c431891002212ab067dd5 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-8184bb6cdf1c431891002212ab067dd52025-01-31T05:12:12ZengElsevieriScience2589-00422025-02-01282111833Adenylate cyclase 10 promotes brown adipose tissue thermogenesisAnupam Das0Christine Mund1Eman Hagag2Ruben Garcia-Martin3Eleftheria Karadima4Anke Witt5Mirko Peitzsch6Andreas Deussen7Triantafyllos Chavakis8Thomas Noll9Vasileia Ismini Alexaki10Department of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD), Neuherberg, GermanyDepartment of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Corresponding authorSummary: Brown adipose tissue (BAT) thermogenesis dissipates energy through heat production and thereby it opposes metabolic disease. It is mediated by mitochondrial membrane uncoupling, yet the mechanisms sustaining the mitochondrial membrane potential (ΔΨm) in brown adipocytes are poorly understood. Here we show that isocitrate dehydrogenase (IDH) activity and the expression of the soluble adenylate cyclase 10 (ADCY10), a CO2/bicarbonate sensor residing in mitochondria, are upregulated in BAT of cold-exposed mice. IDH inhibition or ADCY10 deficiency reduces cold resistance of mice. Mechanistically, IDH increases the ΔΨm in brown adipocytes via ADCY10. ADCY10 sustains complex I activity and the ΔΨm via exchange protein activated by cAMP1 (EPAC1). However, neither IDH nor ADCY10 inhibition affect uncoupling protein 1 (UCP1) expression. Hence, we suggest that ADCY10, acting as a CO2/bicarbonate sensor, mediates the effect of IDH on complex I activity through cAMP-EPAC1 signaling, thereby maintaining the ΔΨm and enabling thermogenesis in brown adipocytes.http://www.sciencedirect.com/science/article/pii/S2589004225000938PhysiologyMolecular biologyCell biology |
| spellingShingle | Anupam Das Christine Mund Eman Hagag Ruben Garcia-Martin Eleftheria Karadima Anke Witt Mirko Peitzsch Andreas Deussen Triantafyllos Chavakis Thomas Noll Vasileia Ismini Alexaki Adenylate cyclase 10 promotes brown adipose tissue thermogenesis iScience Physiology Molecular biology Cell biology |
| title | Adenylate cyclase 10 promotes brown adipose tissue thermogenesis |
| title_full | Adenylate cyclase 10 promotes brown adipose tissue thermogenesis |
| title_fullStr | Adenylate cyclase 10 promotes brown adipose tissue thermogenesis |
| title_full_unstemmed | Adenylate cyclase 10 promotes brown adipose tissue thermogenesis |
| title_short | Adenylate cyclase 10 promotes brown adipose tissue thermogenesis |
| title_sort | adenylate cyclase 10 promotes brown adipose tissue thermogenesis |
| topic | Physiology Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225000938 |
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