Watmough 2010 Biochim Biophys Acta
| Watmough NJ, Frerman FE (2010) The electron transfer flavoprotein: ubiquinone oxidoreductases. Biochim Biophys Acta 1797:1910-6. https://doi.org/10.1016/j.bbabio.2010.10.007 |
Watmough NJ, Frerman FE (2010) Biochim Biophys Acta
Abstract: Electron transfer flavoprotein: ubiqionone oxidoreductase (ETF-QO) is a component of the mitochondrial respiratory chain that together with electron transfer flavoprotein (ETF) forms a short pathway that transfers electrons from 11 different mitochondrial flavoprotein dehydrogenases to the ubiquinone pool. The X-ray structure of the pig liver enzyme has been solved in the presence and absence of a bound ubiquinone. This structure reveals ETF-QO to be a monotopic membrane protein with the cofactors, FAD and a [4Fe-4S](+1+2) cluster, organised to suggests that it is the flavin that serves as the immediate reductant of ubiquinone. ETF-QO is very highly conserved in evolution and the recombinant enzyme from the bacterium Rhodobacter sphaeroides has allowed the mutational analysis of a number of residues that the structure suggested are involved in modulating the reduction potential of the cofactors. These experiments, together with the spectroscopic measurement of the distances between the cofactors in solution have confirmed the intramolecular pathway of electron transfer from ETF to ubiquinone. This approach can be extended as the R. sphaeroides ETF-QO provides a template for investigating the mechanistic consequences of single amino acid substitutions of conserved residues that are associated with a mild and late onset variant of the metabolic disease multiple acyl-CoA dehydrogenase deficiency (MADD).
โข Bioblast editor: Gnaiger E
Selected quotes
- During the ฮฒ-oxidation process the two carbon units are removed from long-chain acyl-CoA esters by repeated cycles of oxidation, hydration, oxidation and thiolysis. In each cycle the initial oxidation step is catalysed by one of four chain-length specific FAD-containing dehydrogenases [2โ4]. The identification of the first three of these acyl-CoA dehydrogenases in the 1950s was followed by the identification of the electron transfer flavoprotein (ETF) as their common electron acceptor [5]. A further 20 years elapsed before ETF:ubiquinone oxidoreductase was purified from beef heart mitochondria by Ruzicka and Beinert and shown to mediate electron transfer between ETF and ubiquinone [6]. It is now recognised that the ETF/ETF:QO system serves as a short electron transfer pathway (Fig. 1) to conduct electrons from nine different mitochondrial FAD-containing acyl-CoA dehydrogenases of fatty acid ฮฒ-oxidation and amino acid catabolism to the ubiquinone pool of the main respiratory chain [7,8]. The same pathway also accepts electrons from sarcosine dehydrogenase and dimethylglycine dehydrogenase, two enzymes of mitochondrial one-carbon metabolism [9]. The ubiquinone pool in the inner mitochondrial membrane accessed by ETF:QO is also that accessed by NADH derived from carbohydrate and ketone body (ฮฒ-hydroxybutyrate) oxidation via complex I of the main respiratory chain [10]. This potential for cross-talk may provide the basis for the regulation of fatty acid oxidization by the cytosolic [NAD+]/[NADH] ratio [11,12].
- The mature protein, despite behaving like an integral membrane protein, has no membrane-spanning helices.
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