High membrane potential promotes alkenal-induced mitochondrial uncoupling and influences adenine nucleotide translocase conformation
| Autor: | Martin D. Brand, Vian Azzu, Nadeene Parker |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Protein Conformation
HNE 4-hydroxynonenal Mitochondria Liver Oxidative phosphorylation Mitochondrion Biology Biochemistry Oxidative Phosphorylation Membrane Potentials 03 medical and health sciences Oxygen Consumption ROS reactive oxygen species CAtr carboxyatractylate Animals Translocase ANT adenine nucleotide translocase Inner mitochondrial membrane Molecular Biology 030304 developmental biology Membrane potential Aldehydes 0303 health sciences Nucleotides 030302 biochemistry & molecular biology Biological Transport Cell Biology carboxyatractylate (CAtr) TPMP triphenylmethylphosphonium Mitochondria Rats Kinetics 4-hydroxynonenal (HNE) trypsin FCCP carbonyl cyanide p-trifluoromethoxyphenylhydrazone Translocase of the inner membrane Biophysics biology.protein Female ATP–ADP translocase Protons UCP uncoupling protein Intermembrane space Mitochondrial ADP ATP Translocases rat liver mitochondrion Research Article proton leak |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20080321 |
| Popis: | Mitochondria generate reactive oxygen species, whose downstream lipid peroxidation products, such as 4-hydroxynonenal, induce uncoupling of oxidative phosphorylation by increasing proton leak through mitochondrial inner membrane proteins such as the uncoupling proteins and adenine nucleotide translocase. Using mitochondria from rat liver, which lack uncoupling proteins, in the present study we show that energization (specifically, high membrane potential) is required for 4-hydroxynonenal to activate proton conductance mediated by adenine nucleotide translocase. Prolonging the time at high membrane potential promotes greater uncoupling. 4-Hydroxynonenal-induced uncoupling via adenine nucleotide translocase is prevented but not readily reversed by addition of carboxyatractylate, suggesting a permanent change (such as adduct formation) that renders the translocase leaky to protons. In contrast with the irreversibility of proton conductance, carboxyatractylate added after 4-hydroxynonenal still inhibits nucleotide translocation, implying that the proton conductance and nucleotide translocation pathways are different. We propose a model to relate adenine nucleotide translocase conformation to proton conductance in the presence or absence of 4-hydroxynonenal and/or carboxyatractylate. |
| Databáze: | OpenAIRE |
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