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Dibutyltin‐3‐hydroxyflavone titrates a dissociable component (cofactor) of mitochondrial ATP synthase: An energy‐transfer component linked to the ubiquinone pool
Author(s) -
Griffiths David E.
Publication year - 1994
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.590080210
Subject(s) - submitochondrial particle , chemistry , atp synthase , atpase , oxidative phosphorylation , cofactor , biochemistry , stereochemistry , titration , mitochondrion , enzyme , inorganic chemistry
Dibutyltin‐3‐hydroxyflavone, Bu 2 Sn(of), is a new fluorescence probe inhibitor of F 1 F 0 ‐ATPase and oxidative phosphorylation which inhibits by titration of an unidentified component of F 0 . Its site of action is closely related to that of the trialkyltins and of venturicidin. This F 0 component is part of a pool of this component which is present in the heart mitochondrial inner membrane at levels of 5–7 nmol (mg protein) −1 [18 ± 3 Bu 2 Sn(of) sites per mol F 1 F 0 ‐ATPase]. However, ATPase activity in submitochondrial particles is near maximally inhibited by titration of approx. three Bu 2 Sn(of) sites per mol F 1 F 0 ‐ATPase. Over 60% (60–80%) of the Bu 2 Sn(of) interaction sites can be lost during the purification of F 1 F 0 ‐ATPase from submitochondrial particles. The number of Bu 2 Sn(of) interaction sites in various F 1 F 0 ‐ATPase preparations is variable. The high numbers of Bu 2 Sn(of) sites per mol F 1 F 0 ‐ATPase for heart mitochondria (18–21) and submitochondrial particles (15–19.5) decline in ATP synthase (11–15) to the low values obtained in Complex V (7–10.5) and the minimal values observed in highly purified F 1 F 0 −ATPase (3.5–5.6), thus indicating a variable dissociable component or cofactor of ATP synthase. The Bu 2 Sn(of) interaction site, a component of ATP synthase, is responsive to the redox status of the respiratory chain and the interaction with Bu 2 Sn(of) is with the reduced form of this component. Fluorescence titration studies show that this component is in redox equilibrium with the ubiquinone pool of the respiratory chain. It is proposed that this redox component serves as an inhibitor titratable cofactor pool which cycles through an F 0 interaction site (or sites) via a system which serves as an energy‐transfer link between the respiratory chain and ATP synthase.