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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.
- Source :
-
Journal of bioenergetics and biomembranes [J Bioenerg Biomembr] 2012 Oct; Vol. 44 (5), pp. 525-38. Date of Electronic Publication: 2012 Jul 14. - Publication Year :
- 2012
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Abstract
- 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.
- Subjects :
- Membrane Potential, Mitochondrial drug effects
Oxidation-Reduction drug effects
Uncoupling Protein 1
Acanthamoeba castellanii metabolism
Aldehydes pharmacology
Cysteine Proteinase Inhibitors pharmacology
Guanosine Triphosphate metabolism
Ion Channels metabolism
Mitochondria metabolism
Mitochondrial Proteins metabolism
Protozoan Proteins metabolism
Ubiquinone metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6881
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of bioenergetics and biomembranes
- Publication Type :
- Academic Journal
- Accession number :
- 22798183
- Full Text :
- https://doi.org/10.1007/s10863-012-9456-x