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

Gong, Xing; Yu, Linda; Xia, Di; Yu, Chao

doi:10.1074/jbc.m409994200

Cited by 51 publications

(35 citation statements)

References 40 publications

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“…Mitochondrial complex III forms a dimer in the crystal structures of the bovine (2), chicken (31), and yeast (32) enzymes. The crystal structures suggest that the complex is functional as a dimer, which is supported by data showing that the two monomers differ in their cytochrome c binding properties and their ubiquinone reduction sites (33) and that electrons are transferred between equivalent hemes in the two monomers (34). The fact that a complex III dimer is seen in the supercomplexes of both bovine heart (this work) and plant mitochondria (20) strongly supports the existence of a functional dimer for complex III.…”

Section: Discussionsupporting

confidence: 66%

Architecture of Active Mammalian Respiratory Chain Supercomplexes

Schäfer

Seelert

Reifschneider

et al. 2006

Journal of Biological Chemistry

253

187

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In the inner mitochondrial membrane, the respiratory chain complexes generate an electrochemical proton gradient, which is utilized to synthesize most of the cellular ATP. According to an increasing number of biochemical studies, these complexes are assembled into supercomplexes. However, little is known about the architecture of the proposed multicomplex assemblies. Here, we report the electron microscopic characterization of the two respiratory chain supercomplexes I 1 III 2 and I 1 III 2 IV 1 in bovine heart mitochondria, which are also two major supercomplexes in human mitochondria. After purification and demonstration of enzymatic activity, their structures in projection were determined by single particle image analysis. A difference map between the supercomplexes I 1 III 2 and I 1 III 2 IV 1 closely fits the x-ray structure of monomeric complex IV and shows its location in the assembly. By comparing different views of supercomplex I 1 III 2 IV 1 , the location and mutual arrangement of complex I and the complex III dimer are discussed. Detailed knowledge of the architecture of the active supercomplexes is a prerequisite for a deeper understanding of energy conversion by mitochondria in mammals.All living organisms use a series of integral membrane protein complexes for energy conversion and ATP synthesis. In eukaryotes, electrons are transported by the respiratory chain, starting from NADH via complex I (NADH:ubiquinone oxidoreductase) or from succinate via complex II (succinate:ubiquinone oxidoreductase), the membrane integral electron carrier ubiquinol, complex III (ubiquinol:cytochrome c oxidoreductase), the peripheral electron carrier cytochrome c, and complex IV (cytochrome c oxidase) to the terminal acceptor molecular oxygen (1). The electron transport chain generates a proton gradient across the inner mitochondrial membrane, which is used by complex V (F O F 1 -ATP synthase) to synthesize ATP. In the last decade, structures of the individual respiratory chain complexes from various organisms have been determined. Atomic models exist for bovine heart mitochondrial complex III (2) and IV (3). A high resolution structure of complex I is not yet available, but electron microscopy indicates that it is L-shaped in all organisms investigated, and a 2.2-nm resolution map from cryoelectron microscopy exists for the bovine heart complex I (4).Two alternative models for the arrangement of the respiratory chain complexes in the membrane have been proposed. According to the currently favored random collision model (5), all components of the respiratory chain diffuse individually in the membrane, and electron transfer depends on the random, transient encounter of the individual protein complexes and the smaller electron carriers. In the solid state model (6) proposed 50 years ago, the substrate is channeled directly from one enzyme to the next. Recently isolated stoichiometric assemblies, so-called supercomplexes, support this model. Respiratory supercomplexes of different compositions have been described in bact...

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Section: Discussionsupporting

confidence: 66%

Architecture of Active Mammalian Respiratory Chain Supercomplexes

Schäfer

Seelert

Reifschneider

et al. 2006

Journal of Biological Chemistry

253

187

View full text Add to dashboard Cite

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“…While the existence of this connection has been considered since the first crystal structures of cytochrome bc 1 were solved (50,55,61,110,199,234,269), the experimental evidence for it was not available until recently. It came from mutagenic studies demonstrating that the derivatives of the enzyme with inactivated Q o site in one monomer and Q i site in the other (cross-inactivated forms) are able to support enzymatic turnover using effectively the heme b L -b L electron transfer as the only available connection linking the functional Q o and Q i sites (67,68,150,244).…”

Section: H-shaped Electron Transfer System In Dimer and Its Physimentioning

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

140

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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“…production mediated by low potential cytochrome b L (or b 566 ) was postulated as shown in the Q cycle pathway ( Fig. 1) (13,14), whereas the importance of this autoxidation mediated by the ferrocytochrome b moiety in overall O 2 . generation remains unclear.…”

Section: Spin-trapping Technique Using Depmpo (5-mentioning

confidence: 99%