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

Abstract

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.

Metastable radical state, nonreactive with oxygen, is inherent to catalysis by respiratory and photosynthetic cytochromes bc 1 / b 6 f

“…1A) generate a proton-motive force (pmf) that powers cellular metabolism by using the Gibbs free energy difference (ΔG) between hydroquinone (QH 2 ) derivatives (Fig. 1B) and oxidized soluble electron transfer proteins (e.g., cytochrome c or plastocyanin) (1,2). To increase the efficiency of this process, which is critical for the yield of the generated pmf, one part of the enzyme recirculates electrons to the quinone pool in the membrane (Q pool), whereas the second part steers the electrons to the cytochrome c pool, powering the electron recirculation (Fig.…”

Dysfonctions mitochondriales et vieillissement musculaire

“…4 Les mitochondries intermyofibrillaires sont localisées entre les myofibrilles. 5 Les mitochondries sous-sarcolemmales sont localisées juste sous la membrane des cellules musculaires. mécanismes impliqués restent, à l'heure actuelle, encore incompris, des études récentes suggèrent qu'une réduction du potentiel mitophagique et qu'une altération de la dynamique et de la morphologie des mitochondries pourraient être impliquées dans cette accumulation de dysfonctions au cours du vieillissement.…”

“…Un des changements les plus délétères et les plus caractéristiques, associés au vieillissement normal, se de NADH,H + qui pourrait, au travers de l'augmentation d'activité du complexe I qu'elle peut induire, augmenter le taux de réduction des pools de quinones et de cytochrome C, et, ainsi, favoriser la production d'EAO par la chaîne respiratoire [5]. L'entrée de calcium dans la mitochondrie dépend principalement du canal à anions dépendant du voltage (VDAC), qui permet aux ions de traverser la membrane externe mitochondriale, et de l'uniport calcique qui favorise la traversée de la membrane interne du calcium [6].…”

Redox chemistry of coenzyme Q—a short overview of the voltammetric features

“…During the occurrence of the electron and proton transfer reactions in the METC, Coenzyme Q 10 turns between fully oxidized form-quinone and fully reduced form-quinol (or ubiquinol). Next to this crucial role in the cell energy creation, there are lots of studies dedicated to many other functions of Coenzyme Q 10 in the living cells [4,5]. It is well known that Coenzyme Q 10 occurs in all subcellular membranes, while having a very important role in functioning of many membrane oxido-reductase systems such as mitochondria, Golgi apparatus, lysosomes, and plasmalemma [1,5].…”

“…Next to this crucial role in the cell energy creation, there are lots of studies dedicated to many other functions of Coenzyme Q 10 in the living cells [4,5]. It is well known that Coenzyme Q 10 occurs in all subcellular membranes, while having a very important role in functioning of many membrane oxido-reductase systems such as mitochondria, Golgi apparatus, lysosomes, and plasmalemma [1,5]. In these systems, Coenzyme Q 10 , via its redox chemistry, influences many pathways in the cells, ranging from pro-oxidant to antioxidant activities (free-radical generation and scavenging of free radicals) and modulating cellular pathology [6][7][8].…”