Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis

Jones, Scott A., Ruprecht, Jonathan J., Crichton, Paul G. ORCID: https://orcid.org/0000-0003-3786-8359 and Kunji, Edmund R.S. (2024) Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis. Trends in Biochemical Sciences. ISSN 0968-0004

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Abstract

In mitochondria, the oxidation of nutrients is coupled to ATP synthesis by the generation of a protonmotive force across the mitochondrial inner membrane. In mammalian brown adipose tissue (BAT), uncoupling protein 1 (UCP1, SLC25A7), a member of the SLC25 mitochondrial carrier family, dissipates the protonmotive force by facilitating the return of protons to the mitochondrial matrix. This process short-circuits the mitochondrion, generating heat for non-shivering thermogenesis. Recent cryo-electron microscopy (cryo-EM) structures of human UCP1 have provided new molecular insights into the inhibition and activation of thermogenesis. Here, we discuss these structures, describing how purine nucleotides lock UCP1 in a proton-impermeable conformation and rationalizing potential conformational changes of this carrier in response to fatty acid activators that enable proton leak for thermogenesis.

Item Type:	Article
Additional Information:	Publisher Copyright: © 2024 The Author(s)
Uncontrolled Keywords:	bioenergetics,brown adipose tissue,non-shivering thermogenesis,slc25 mitochondrial carrier family,thermogenin,ucp1,biochemistry,molecular biology ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	16 Apr 2024 12:30
Last Modified:	16 Apr 2024 12:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/94915
DOI:	10.1016/j.tibs.2024.03.005

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