Teran Torres, Enrique Eduardo;
(2001)
Ubiquinone reacts with nitric oxide to prevent the activity of purified complex 1.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Mitochondrial complex I is a protein of 800 kDa consisting of 41 subunits. It contains flavin mononucleotide (FMN) and between 22-24 iron-sulphur (Fe-S) centres. Complex I is responsible for the oxidation of NADH to NAD+ in the presence of ubiquinone (CoQ) as electron acceptor. In this process, CoQ is reduced to ubiquinol (C0 QH2) which is re-oxidised to CoQ by complex III. Recently, it was shown in intact cells that prolonged exposure to nitric oxide (NO) results in a persistent inhibition of complex I activity, which is preceded by a decrease in the concentration of intracellular glutathione. The objective of this study was to investigate the possible mechanism(s) of the inhibition of complex I by NO using purified complex I from bovine heart mitochondria. The oxidation rate of NADH in the presence of complex I and CoQ was measured as an indicator of complex I activity, and the effect of different NO donors and incubation times on complex I activity was evaluated. Incubation of purified complex I with NO donors revealed no differences in the oxidation rate of NADH as compared to untreated controls. These results suggest that NO does not affect the activity of purified complex I. However, it was found that NADH added serially could be repeatedly oxidised by purified complex I and CoQ. In these conditions, exposure of CoQ to NO resulted in a reduction of the initial NADH oxidation and prevented almost completely the subsequent oxidation. Interestingly, the inhibitory effect of NO on CoQ was temporary and was completely reversible with time, suggesting the formation of a labile NO-CoQ adduct. Further biochemical and pharmacological analysed provided evidence of a chemical reaction between NO and CoQ.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Ubiquinone reacts with nitric oxide to prevent the activity of purified complex 1 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Pure sciences; Mitochondrial complex 1 |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10097315 |
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