Hydroxynonenal, a lipid peroxidation end product, stimulates uncoupling protein activity in Acanthamoeba castellanii mitochondria; the sensitivity of the inducible activity to purine nucleotides depends on the membranous ubiquinone redox state.
We studied the influence of exogenously generated superoxide and exogenous 4-hydroxy-2-nonenal (HNE), a lipid peroxidation end product, on the activity of the Acanthamoeba castellanii uncoupling protein (AcUCP). The superoxide-generating xanthine/xanthine oxidase system was insufficient to induce mitochondrial uncoupling. In contrast, exogenously added HNE induced GTP-sensitive AcUCP-mediated mitochondrial uncoupling. In non-phosphorylating mitochondria, AcUCP activation by HNE was demonstrated by increased oxygen consumption accompanied by a decreased membrane potential and ubiquinone (Q) reduction level. The HNE-induced GTP-sensitive proton conductance was similar to that observed with linoleic acid. In phosphorylating mitochondria, the HNE-induced AcUCP-mediated uncoupling decreased the yield of oxidative phosphorylation. We demonstrated that the efficiency of GTP to inhibit HNE-induced AcUCP-mediated uncoupling was regulated by the endogenous Q redox state. A high Q reduction level activated AcUCP by relieving the inhibition caused by GTP while a low Q reduction level favoured the inhibition. We propose that the regulation of UCP activity involves a rapid response through the endogenous Q redox state that modulates the inhibition of UCP by purine nucleotides, followed by a late response through lipid peroxidation products resulting from an increase in the formation of reactive oxygen species that modulate the UCP activation.
Laboratory of Bioenergetics, Adam Mickiewicz University, Poznan, Poland.
Andrzej M
AM
Woyda-Ploszczyca
Wieslawa
W
Jarmuszkiewicz
D048248:Acanthamoeba castellanii / Q000378:metabolism*; D000447:Aldehydes / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D015800:Protozoan Proteins / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism*; D000071256:Uncoupling Protein 1
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D007473:Ion Channels; D024101:Mitochondrial Proteins; D015800:Protozoan Proteins; D000071256:Uncoupling Protein 1; D014451:Ubiquinone; D006160:Guanosine Triphosphate; C027576:4-hydroxy-2-nonenal