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Das, A.* ; Mund, C.* ; Hagag, E.* ; Garcia-Martin, R.* ; Karadima, E.* ; Witt, A.* ; Peitzsch, M.* ; Deussen, A.* ; Chavakis, T. ; Noll, T.* ; Alexaki, V.I.*

Adenylate cyclase 10 promotes brown adipose tissue thermogenesis.

iScience 28:111833 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cell Biology ; Molecular Biology ; Physiology; Obesity
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 28, Issue: 2, Pages: , Article Number: 111833 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-008
Grants Saxon State Ministry of Science, Culture and Tourism-SMWK (Unterstutzung profilbestimmender Struktureinheiten der TU Dresden)
Deutsche Forschungsgemeinschaft
DOI 10.1016/j.isci.2025.111833
WOS ID 001422270000001
Scopus ID 85216237156
PubMed ID 39949963
Erfassungsdatum 2025-04-01
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