Uncoupling protein 1 inhibition by purine nucleotides is under control of the endogenous ubiquinone redox state

Aleksandra Swida-Barteczka , Andrzej Woyda-Ploszczyca , Francis E. Sluse , Wieslawa Jarmuszkiewicz (1)

1 Laboratory of Bioenergetics

We studied free fatty acid-induced uncoupling of heterologously expressed rat UCP1 in yeast mitochondria as well as UCP1 in rat BAT mitochondria. The proton conductance curves and the relationship between ubiquinone reduction level and membrane potential were determined in non-phosphorylating BAT and yeast mitochondria. The ADP/O method was applied to determine the ADP phosphorylation rate and the relationship between ubiquinone reduction level and respiration rate in yeast mitochondria. Our studies of membranous ubiquinone reduction level in mitochondria demonstrate that activation of UCP1 leads to a purine nucleotide-sensitive decrease in the ubiquinone redox state. Results obtained for non-phosphorylating and phosphorylating mitochondria, as the endogenous ubiquinone redox state was gradually varied by a lowering rate of the ubiquinone-reducing or ubiquinol-oxidising pathways, indicate that the endogenous ubiquinone redox state has no effect on free fatty acid-induced UCP1 activity in the absence of GTP, and can only regulate this activity through sensitivity to inhibition by the purine nucleotide. At a given oleic acid concentration, inhibition by GTP diminishes when ubiquinone is reduced sufficiently. The ubiquinone redox state-dependent alleviation of UCP1 inhibition by the purine nucleotide was observed at a high ubiquinone reduction level, when it exceeded 85-88%.

Mots clés: Life Sciences

Aleksandra Swida-Barteczka, Andrzej Woyda-Ploszczyca, Francis E. Sluse, Wieslawa Jarmuszkiewicz. Uncoupling protein 1 inhibition by purine nucleotides is under control of the endogenous ubiquinone redox state. Biochemical Journal, 2009, 424 (2), pp.297-306. ⟨10.1042/BJ20091158⟩. ⟨hal-00479239⟩