Login
- Title:
Comparative analysis of human and murine Uncoupling Protein 1 reveals essential structural features of human UCP1
- Document type:
- Forschungsdaten
- Publication date:
- 06.08.2024
- Responsible:
- Klingenspor, Martin
- Authors:
- Musiol, Eva; Hau, Julia; Di Pizio, Antonella; Fromme, Tobias; Klingenspor, Martin
- Author affiliation:
- TUM
- Publisher:
- TUM
- Identifier:
- doi:10.14459/2024mp1740589
- End date of data production:
- 31.10.2023
- Subject area:
- BIO Biowissenschaften; MED Medizin; OEK Ökotrophologie, Ernährungswissenschaft
- Resource type:
- Experimente und Beobachtungen / experiments and observations; Abbildungen von Objekten / image of objects; Statistik und Referenzdaten / statistics and reference data
- Data type:
- mehrdimensionale Visualisierungen oder Modelle / models; Texte / texts; Tabellen / tables
- Description:
- Background:
Mitochondrial uncoupling protein 1 (UCP1) is a unique protein of brown adipose tissue. Upon activation by free fatty acids, UCP1 facilitates a thermogenic net proton flux across the mitochondrial inner membrane. Non-complexed purine nucleotides inhibit this fatty acid-induced activity of UCP1. By far the most available data have been generated from rodent model systems. In the light of being a putative pharmacological target for the treatment of metabolic disease, specific aspects of human UCP1 function and its comparability to rodent orthologues are of importance.
Methods:
In the present study, we established a doxycycline-regulated cell model with inducible human or murine UCP1 expression and conducted functional studies using respirometry.
Results:
We demonstrate that human and murine UCP1 exhibit similar specific fatty acid-induced activity, but divergent inhibitory potential of purine nucleotides. Mutagenesis of non-conserved residues in human UCP1 revealed structural components in α-helix 56 and α-helix 6 crucial for uncoupling function.
Conclusions:
A deeper structure-function analysis of UCP1 is not only essential to understand its unique function but is also needed in the search for new UCP1 activators. - Method of data assessment:
- The data were acuired by cell culture of the human embryonic kidney cell line HEK293. These cells were genetically modified using flip recombinase to express different versions of mouse and human uncoupling protein 1 (UCP1 wildtype, epitope-tagged, mutant). UCP1 expression was induced using a TET-On system and UCP1 expression level, intracellular localization and uncoupling activity measured by Western blot analyses, immunoflourescence microscopy, and respirometry, respectively.
- Links:
- This dataset relates to the publication: https://onlinelibrary.wiley.com/doi/10.1111/apha.14209
- Key words:
- thermogenesis; brown adipose tissue; uncoupling proteins; mitochondria
- Technical remarks:
- View and download (4,62 MB total, 11 Files)
The data server also offers downloads with FTP
The data server also offers downloads with rsync (password m1740589):
rsync rsync://m1740589@dataserv.ub.tum.de/m1740589/ - Language:
- en
BibTeX