Anti-cooperative Oxidation of Ubiquinol by the Yeast Cytochrome bc1 Complex

Covián, Raúl; Gutiérrez-Cirlos, Emma Berta; Trumpower, Bernard L.

doi:10.1074/jbc.m400193200

Cited by 53 publications

(83 citation statements)

References 33 publications

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“…At pH 7, the E m of the Rieske protein in wild-type QCR is ϳ15 mV higher than that of cytochrome c 1 . As a result, the cytochrome c 1 will not be completely reduced during the first turnover, since the electron that is transferred into the high potential chain from the quinol will equilibrate to the Rieske protein (26). At pH 8.8, the E m of the Rieske protein is about 70 mV lower than that of cytochrome c 1 , resulting in ϳ80% reduction of the c 1 heme during the first pre-steady-state turnover of the enzyme.…”

Section: Pre-steady-state Reduction Kinetics Of Qcrs With Mutations Imentioning

confidence: 99%

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Wenz

Covián

Hellwig

et al. 2007

Journal of Biological Chemistry

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The cytochrome bc 1 complex is a dimeric enzyme of the inner mitochondrial membrane that links electron transfer from ubiquinol to cytochrome c by a protonmotive Q cycle mechanism in which ubiquinol is oxidized at one center in the enzyme, referred to as center P, and ubiquinone is rereduced at a second center, referred to as center N. To better understand the mechanism of ubiquinol oxidation, we have examined catalytic activities and pre-steady-state reduction kinetics of yeast cytochrome bc 1 complexes with mutations in cytochrome b that we expected would affect oxidation of ubiquinol. We mutated two residues thought to be involved in proton conduction linked to ubiquinol oxidation, Tyr 132 and Glu 272 , and two residues proposed to be involved in docking ubiquinol into the center P pocket, Phe

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Section: Pre-steady-state Reduction Kinetics Of Qcrs With Mutations Imentioning

confidence: 99%

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Wenz

Covián

Hellwig

et al. 2007

Journal of Biological Chemistry

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“…While this long-range structural effect has been exploited by various models that propose allostery within the dimer of cytochrome bc 1 (50,(52)(53)(54), the origin and the time domain of this inhibitorinduced effect are unknown.…”

Section: Considering the Reversibility Of Reactions Usq Imentioning

confidence: 99%

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Sarewicz

Osyczka

2015

Physiological Reviews

133

141

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Physiol Rev 95: 219 -243, 2015; doi:10.1152/physrev.00006.2014.-Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc 1 or ubiquinol: cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc 1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc 1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria.

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“…The fact that disruption of electron transfer between two b L hemes of dimeric complex causes a decrease of activity indicates that both monomers are not function independently, some sort of negative cooperativity does exist (9).…”

Section: Figmentioning

confidence: 99%

Evidence for Electron Equilibrium between the Two Hemes bL in the Dimeric Cytochrome bc1 Complex

Gong

Xia

et al. 2005

Journal of Biological Chemistry

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The cytochrome bc 1 complex (also known as ubiquinol-cytochrome c reductase or Complex III) is an essential segment of the electron transfer chains of mitochondria and many respiratory and photosynthetic bacteria (1). It catalyzes electron transfer from ubiquinol to cytochrome c with concomitant translocation of protons across the membrane to generate a proton gradient and membrane potential for ATP synthesis. The "proton-motive Q-cycle" is the most favored mechanism for electron and proton transfer in this complex (2, 3). The central feature of the Q-cycle mechanism is the bifurcation of electrons from ubiquinol at the Qo site. The first electron of ubiquinol is transferred to the "high potential chain," consisting of the Rieske [2Fe-2S] cluster, housed in the iron-sulfur protein (ISP), 1 and heme c 1 , housed in cytochrome c 1 . Then the second electron of ubiquinol is passed through the "low potential chain" consisting of heme b L and heme b H , both housed in the cytochrome b subunit.Recently, mitochondrial cytochrome bc 1 complexes from beef (4, 5), chicken (6), and yeast (7) were crystallized, and their three-dimensional structures were determined. The structural information not only supports the Q-cycle mechanism but also suggests the complex functioning as a dimer. This suggestion stems from the following structural data (4 -7): (i) the intertwining of ISPs in the two bc 1 monomers such that the head domain of ISP in one monomer is physically close to and interacting with the cytochrome b and cytochrome c 1 in the 2-fold symmetry-related other monomer; (ii) the presence of two apparently non-communicating cavities in the dimeric complex, each connecting the Qo pocket of one monomer to the Qi pocket of the other; and (iii) the distance between the Fe atoms of the two hemes b L is only 21 Å, which is approximately the same as that between heme b L and b H in one monomer (Fig. 1). The short distance between the two hemes b L and the presence of several aromatic amino acid residues at the interface of the two cytochrome b proteins has promoted investigator to speculate the existence of electron transfer or equilibrating between the two hemes b L (8 -10). Recently the existence of an intertwined dimer in solution was confirmed (11) in the Rhodobacter sphaeroides bc 1 complex through the formation of a four-subunit (two ISPs and two cytochrome bs) adduct by two inter-subunit disulfide bonds between two engineered cysteine pairs: one at cytochrome b and the head domain of ISP and the other at cytochrome b and the tail domain of ISP. However, evidence for inter-monomer b L -b L electron transfer during bc 1 catalysis is still missing, due to the lack of a suitable assay method.It has been reported that during electron transfer through the bc 1 complex, superoxide anion (O 2 . ) is produced (12-18).This results from a leakage of the second electron of ubiquinol, from the low potential chain of the Q cycle electron transfer pathway, to interact with molecular oxygen. The electron-leaking site is thought to be lo...

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Anti-cooperative Oxidation of Ubiquinol by the Yeast Cytochrome bc1 Complex

Cited by 53 publications

References 33 publications

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Mutational Analysis of Cytochrome b at the Ubiquinol Oxidation Site of Yeast Complex III

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

Evidence for Electron Equilibrium between the Two Hemes bL in the Dimeric Cytochrome bc1 Complex

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