Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis

Trends Biochem Sci. 2024 Apr 1:S0968-0004(24)00071-9. doi: 10.1016/j.tibs.2024.03.005. Online ahead of print.ABSTRACTIn 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.PMID:38565497 | DOI:10.1016/j.tibs.2024.03.005
Source: Trends in Biochemical Sciences - Category: Biochemistry Authors: Source Type: research