Mitochondrial redox component

The final group of mitochondrial redox components are one-electron carriers, small proteins (cytochromes) that contain iron in the form of the porphyrin complex known as heme. These carriers, which are discussed in Chapter 16, exist as several chemically distinct types a, b, and c. Two or more components of each type are present in mitochondria. The complex cytochrome aa3 deserves special comment. Although cytochromes are single-electron carriers, the cytochrome aa3 complex must deliver four electrons to a single 02 molecule. This may explain why the monomeric complex contains two hemes and two copper atoms which are also able to undergo redox reactions.1 2... 

Chazotte, B., and Hackenbrock, C.R. (1991) Lateral diffusion of redox components in the mitochondrial inner membrane is unaffected by inner membrane folding and matrix density./. Biol. Chem. 266, 5973. 

Inhibition of whole chain electron transport can result from (a) Interaction of the inhibitor with a redox component of the pathway or (b) interaction with carrier systems that transport substrate molecules across the inner membrane. The latter interaction could be direct or indirect. Because electron transport associated with the oxidation of malate, succinate, and exogenous NADH were all inhibited, but to differing extents, a specific Interaction with a single redox component of the inner mitochondrial membrane does not seem to be involved. 

Lenaa, G. fl9S8), Role of mobility of redox components in the inner mitochondrial mem brans. /. M Fnfjr Biol. 104,193i-2[)9. 

The oxidation by 02 of [H] (either as NADH or FADH, succinate or directly as active acetic acid) occurs via a sequence of electron transfer steps between redox components being incorporated (more or less deeply) into the inner mitochondrial membrane. As is shown in Fig. 11 in the above mentioned electron transport chain, referred to as respiratory chain, the electronic energy is successively decreased step by step. Oxygen is introduced only into the last step of the chemical events in the respiratory chain. Nature has developed a special enzyme system, the cytochrome oxidase, for the realization of oxygen reduction to water. It is assumed that this enzyme system provides the indispensible cooperation of four electrons and protons, respectively, which is required for oxygen reduction ... 

It is well established that Q is a component of the respiratory chain and plays a critical role in respiration and oxidative phosphorylation. It was thought that the presence of (X was confined exclusively to the inner mitochondrial membrane and its sole function was to serve as the redox component of the respiratory chain. However, this belief has been modified as it has been shown that Q is present in all cellular membranes examined. The major part of Q is present in the reduced form in human and animal tissues, and serves as an important antioxidant. In fact, it has been shown that QH2-IO, the reduced form of Q IO, efficiently scavenges free radicals and it is as effective as ct-tocopherol in preventing peroxidative damage to lipids, considered the best lipid-soluble antioxidant in humans. The antioxidant and prooxidant properties of mitochondrial ubiquinone have recently been reviewed. ... 

Measurement of the thermodynamic poise of redox components of electron transfer chains under coupled conditions has been used extensively in the mitochondrial field to analyze through "cross-over points" the contributions to different spans to the work required to drive ATP synthesis, or maintain the proton gradient. In the work described in this paper, a steady state approach has been developed by which the redox poise of the electron transfer chain, the electron flux and H -gradient could be simultaneously monitored, and the approach to the coupled steady-state (static head) could be followed kinetically on illumination of chromatophores from Rhodobacter sphaeroides. 

Q-cyde a cycle devised by P. Mitchell [FEBS Lett. 56 (1975) 1-6 S9 (1975) 137-139] to overcome the requirement of the redox loop mechanism (see Che-miosmotic hypothesis) for a H electron carrier in the cytochrome hq-containing Complex III of the mitochondrial electron transport chain, the Q.c. proposed that ubiquinone (coenzyme Q), the only mobile, hydrophobic redox component of the chain, participates in electron transfer from cytochrome b to cytochrome c, within Complex III by one-electron steps involving the fully reduced quinol-form (QH2), a stabilized free-radical semiquinone-form (QH ) and the fully oxidized quinone-form (Q). It also made use of the observation that cytochrome b appears to be a dimer composed of b- (b and b (b, which is buried deeply in the membrane with probably on the cytosolic side and by. on the matrix side. In the Hg., outlining the proposed mechanism, it can be seen that two protons are pumped across the membrane (steps 1 9 for uptake from the matrix and steps 3... 

Cyt c is one of most important and extensively studied electron-transfer proteins, partly because of its high solubility in water compared with other redox-active proteins. In vivo, cyt c transfers an electron from complex III to complex IV, membrane-bound components of the mitochondrial electron-transfer chain. The electrochemical interrogation of cyt c has, however, been hindered because the redox-active heme center is... 

To explain how H+ transfer occurred across the membrane Mitchell suggested the protons were translocated by redox loops with different reducing equivalents in their two arms. The first loop would be associated with flavoprotein/non-heme iron interaction and the second, more controversially, with CoQ. Redox loops required an ordered arrangement of the components of the electron transport system across the inner mitochondrial membrane, which was substantiated from immunochemical studies with submitochondrial particles. Cytochrome c, for example, was located at the intermembranal face of the inner membrane and cytochrome oxidase was transmembranal. The alternative to redox loops, proton pumping, is now known to be a property of cytochrome oxidase. 

L-selegiline alters the redox state of ubiquinone, suggesting that the flow of electrons is impaired in the respiratory chain. Furthermore, a decrease in ubiquinone levels has been observed, whereas ubiquinol (reduced ubiquinone) concentrations are increased in the striatum. Ubiquinol levels have been shown to augment as a result of impaired mitochondrial respiration. For example, ubiquinol concentrations were demonstrated to increase in tubular kidney cells exposed to complex IV inhibitors and in disease states with defects in respiratory chain components. These results are also consistent with the hypothesis that L-selegiline enhances 02 formation by altering the rate of electron transfer within the respiratory chain leading to increases in SOD activities in the mouse striatum. 

Fig. 5.3. The major components involved in mitochondrial NADH oxidation in facultative anaerobic mitochondria. In anaerobically functioning mitochondria, NADH is oxidized either by soluble enzymes (left) or by membrane-bound complexes of the electron-transport chain (middle). Under aerobic conditions, a classic respiratory chain is used to oxidize NADH (right). Proton translocation is indicated by H with arrows. Ovals represent the electron transporters RQ, UQ and cytochrome c (cyt. c), and electron transport is indicated by dashed arrows. The vertical bar represents a scale for the standard redox potentials in millivolts. Fum fumarate, NADH-DH NADH dehydrogenase, NADH-ECR soluble NADH enoyl-CoA reductase, RQH2 rhodoquinol, Succ succinate, UQH2 ubiquinol...

Ferredoxins are involved in many microbial redox reactions as well as in mitochondrial hydroxylation reactions in mammals. They are also components of complexes I, II, and III, but not complex IV. 

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