Oxidative Phosphorylation: A Role for Lipoic Acid and Unsaturated Fatty Acids

Abstract

Studies of the mode of action of dibutylchloromethyltin chloride have shown that it reacts with a lipoic acid moiety present in high concentrations in the mitochondrial inner membrane and which is also present in stoicheiometric amounts in purified ATP synthase preparations (3-611101 of lipoic acid/mol of ATP synthase) (Griffiths, 1976a,b). This component has not been characterized, but has the properties of an ester of lipoic acid with an unidentified lipid component. The presence of large amounts of lipoic acid residues that are distinct from the protein-bound lipoic acid moieties of thepyruvateand a-oxoglutarate dehydrogenase complexes, together with evidence that the inhibitors Vol. 5

Studies of energy‐linked reactions: Dihydrolipoate‐ and oleate‐ dependent ATP synthesis in yeast promitochondria

“…Previous experiments indicate that the respiratory chain is not necessary for dihydrolipoate-dependent ATP synthesis [3,4] as the reaction occursin the presence of rotenone and antimycin A and the present experiments with promitochondria appear to confirm that the cytochromes and ubiquinone are not involved. However, the redox reactions involved in dihydrolipoate-dependent ATP synthesis have not been characterised nor has the redox couple which is the electron acceptor in this reaction.…”

“…A similar specificity has been reported by Walenga and Lands [ 111 in their studies of the growth yield of an unsaturated fatty acid auxotroph [ 121 on a variety of unsaturated fatty acids. The specific requirement for an unsaturated fatty acid for ATP synthesis in promitochondria reported here and the previous demonstration of a requirement for an unsaturated fatty acid for ATP synthesis by ATP synthase preparations [3,4] provide an explanation for the inability of UFA auxotrophs of E.coZi [ 131 and yeast [ 1 l] to grow on oxidisable substrates as well as the effects of UFA depletion on oxidative phosphorylation in mitochondria from the UFA auxotroph KD115 [ 141.…”

“…A possible role for ATP-generating reactions in promitochondria and in yeast 'petite' mitochondria has been discussed by Kovac [lo] on the basis of sensitivity to inhibitors and studies of cytochrome de& cient mutants. Detailed examination of dihydrolipoatedependent, oleoyl-S-lipoate-dependent and oleoyl phosphate-dependent ATP synthesis [3,4] in mitochondrial 'petite' mutants, nuclear 'petite' mutants and mitochondrial mit-mutants with specific deletions in cytochrome content and ATPase subunits should be of value in determining the components involved as well as establishing their biogenetic origin.…”

QTL mapping suggests that both cytochrome P450-mediated detoxification and target-site resistance are involved in fenbutatin oxide resistance in Tetranychus urticae

“…The hydrophilic F1 motor catalyzes ATP-synthesis or hydrolysis through a rotary mechanism while the membranous FO motor consists of the static subunits a, b2 and a rotational ring of subunits c, catalyzing ion translocation across the membrane (Wittig and Schagger, 2008). For eukaryotic species, subunit c of the FO motor was postulated as the binding-site of organotin compounds (Griffiths and Hyams, 1977), but using tritium-labeled tributyltin-chloride, Von Ballmoos et al claimed that subunit a of the FO motor is the primary binding site of tributyltin in a bacterial species (von Ballmoos et al, 2004). Target-site insensitivity towards organotin acaricides has been investigated to some extent in spider mites.…”

Pyruvate Dehydrogenase Activity in the Liver, Brain and Adipose-Tissue of Lipid-Deprived Developing Rats. Effect of Minute Amounts of Polyunsaturated Fatty Acids

“…Because of its influence on the structure and fluidity of the subcellular and particular phospholipids Counis & Jutisz, 1977), the proportion of unsaturated (UFAs) and of polyunsaturated (PUFAs) fatty acids affect the transport of substances t h r o u g h the cellular m e m b r a n e s (Kaduce et al, 1977). Moreover, our previous observations clearly suggest that the UFAs and PUFAs could be also involved in the various processes of the intermediary metabolism -and also allows a parallel with the requirement of UFAs which was found in a series of energy-linked reactions (Griffiths, 1976;Griffiths & Hyams, 1977). Furthermore, oleic acid (C18:l) and EFAs were also observed to be used in the biosynthesis of lipoic acid in the developing rat tissues (Carreau et al, 1975(Carreau et al, , 1977(Carreau et al, , 1979, indicating the possible participation of these longchain fatty acids in the construction of the PDH multienzyme complex, and especially in the synthesis of this covalently bound coenzyme.…”