Stimulation of mitochondrial proton conductance by hydroxynonenal requires a high membrane potential
| Autor: | Martin D. Brand, Antonio Vidal-Puig, Nadeene Parker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Mitochondrial ROS
HNE 4-hydroxynonenal Mitochondrion Biochemistry Antioxidants Ion Channels Membrane Potentials Mice 0302 clinical medicine Uncoupling Protein 3 ANT adenine nucleotide translocase WT wild-type Uncoupling Protein 1 Urocortins UCP3 chemistry.chemical_classification Membrane potential 0303 health sciences adenine nucleotide translocase (ANT) Thermogenin Cell biology Mitochondria UCP uncoupling protein uncoupling protein 3 (UCP3) Biophysics Oxidative phosphorylation Biology Models Biological Mitochondrial Proteins 03 medical and health sciences ROS reactive oxygen species Animals Muscle Skeletal Molecular Biology Ion channel 030304 developmental biology Reactive oxygen species Original Paper Aldehydes KO knockout Cell Biology TPMP triphenylmethylphosphonium Rats 4-hydroxynonenal (HNE) chemistry Lipid Peroxidation Reactive Oxygen Species Mitochondrial ADP ATP Translocases 030217 neurology & neurosurgery proton leak |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | Mild uncoupling of oxidative phosphorylation, caused by a leak of protons back into the matrix, limits mitochondrial production of ROS (reactive oxygen species). This proton leak can be induced by the lipid peroxidation products of ROS, such as HNE (4-hydroxynonenal). HNE activates uncoupling proteins (UCP1, UCP2 and UCP3) and ANT (adenine nucleotide translocase), thereby providing a negative feedback loop. The mechanism of activation and the conditions necessary to induce uncoupling by HNE are unclear. We have found that activation of proton leak by HNE in rat and mouse skeletal muscle mitochondria is dependent on incubation with respiratory substrate. In the presence of HNE, mitochondria energized with succinate became progressively more leaky to protons over time compared with mitochondria in the absence of either HNE or succinate. Energized mitochondria must attain a high membrane potential to allow HNE to activate uncoupling: a drop of 10–20 mV from the resting value is sufficient to blunt induction of proton leak by HNE. Uncoupling occurs through UCP3 (11%), ANT (64%) and other pathways (25%). Our findings have shown that exogenous HNE only activates uncoupling at high membrane potential. These results suggest that both endogenous HNE production and high membrane potential are required before mild uncoupling will be triggered to attenuate mitochondrial ROS production. |
| Databáze: | OpenAIRE |
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