Mitochondrial Complex I superoxide production is attenuated by uncoupling
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
18358763
DOI
10.1016/j.biocel.2008.02.007
PII: S1357-2725(08)00075-7
Knihovny.cz E-resources
- MeSH
- Amiloride analogs & derivatives pharmacology MeSH
- Models, Biological MeSH
- Cell Respiration drug effects MeSH
- Mitochondria, Liver drug effects enzymology MeSH
- Rats MeSH
- Glutamic Acid pharmacology MeSH
- Succinic Acid pharmacology MeSH
- Malates pharmacology MeSH
- Hydrogen Peroxide metabolism MeSH
- Rats, Wistar MeSH
- Proton Pumps metabolism MeSH
- Electron Transport Complex I metabolism MeSH
- Uncoupling Agents pharmacology MeSH
- Superoxides metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amiloride MeSH
- ethylisopropylamiloride MeSH Browser
- Glutamic Acid MeSH
- Succinic Acid MeSH
- Malates MeSH
- malic acid MeSH Browser
- Hydrogen Peroxide MeSH
- Proton Pumps MeSH
- Electron Transport Complex I MeSH
- Uncoupling Agents MeSH
- Superoxides MeSH
Complex I, i.e. proton-pumping NADH:quinone oxidoreductase, is an essential component of the mitochondrial respiratory chain but produces superoxide as a side-reaction. However, conditions for maximum superoxide production or its attenuation are not well understood. Unlike for Complex III, it has not been clear whether a Complex I-derived superoxide generation at forward electron transport is sensitive to membrane potential or protonmotive force. In order to investigate this, we used Amplex Red for H(2)O(2) monitoring, assessing the total mitochondrial superoxide production in isolated rat liver mitochondria respiring at state 4 as well as at state 3, namely with exclusive Complex I substrates or with Complex I substrates plus succinate. We have shown for the first time, that uncoupling diminishes rotenone-induced H(2)O(2) production also in state 3, while similar attenuation was observed in state 4. Moreover, we have found that 5-(N-ethyl-N-isopropyl) amiloride is a real inhibitor of Complex I H(+) pumping (IC(50) of 27 microM) without affecting respiration. It also partially prevented suppression by FCCP of rotenone-induced H(2)O(2) production with Complex I substrates alone (glutamate and malate), but nearly completely with Complexes I and II substrates. Sole 5-(N-ethyl-N-isopropyl) amiloride alone suppressed 20% and 30% of total H(2)O(2) production, respectively, under these conditions. Our data suggest that Complex I mitochondrial superoxide production can be attenuated by uncoupling, which means by acceleration of Complex I H(+) pumping due to the respiratory control. However, when this acceleration is prevented by 5-(N-ethyl-N-isopropyl) amiloride inhibition, no attenuation of superoxide production takes place.
References provided by Crossref.org
Mitochondrial Physiology of Cellular Redox Regulations
Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling
Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension
Redox homeostasis in pancreatic β cells
