Mitochondrial electron carriers

Chen et al. [47] demonstrated that the reaction of HOC1 with cytochrome c increased cytochrome peroxidase activity by the oxidation of the methionine residue. Methionine oxidation also significantly decreased the efficiency of cytochrome c as a mitochondrial electron carrier. HOC1, HOBr, and HOI are also able to oxidize (Fen)cytochrome c [48],... 

Table 9.4 Complexes of the mitochondrial electron carriers and ATP generation...

This hypothesis presumes that early free-living prokaryotes had the enzymatic machinery for oxidative phosphorylation and predicts that their modern prokaryotic descendants must have respiratory chains closely similar to those of modern eukaryotes. They do. Aerobic bacteria carry out NAD-linked electron transfer from substrates to 02, coupled to the phosphorylation of cytosolic ADP. The dehydrogenases are located in the bacterial cytosol and the respiratory chain in the plasma membrane. The electron carriers are similar to some mitochondrial electron carriers (Fig. 19-33). They translocate protons outward across the plasma membrane as electrons are transferred to 02. Bacteria such as Escherichia coli have F0Fi complexes in their plasma membranes the F portion protrudes into the cytosol and catalyzes ATP synthesis from ADP and P, as protons flow back into the cell through the proton channel of F0. 

Electrode Potentials of Mitochondrial Electron Carriers and Gibbs Energy Changes Associated with Passage of Electrons3... 

Physiological sources Autoxidation of mitochondrial electron carriers Superoxide dismutases (Cu/Zn-, Mn-) H H ... 

The final step of the reaction involves the transfer of two electrons from iron-sulfur clusters to coenzyme Q. Coenzyme Q is a mobile electron carrier. Its isoprenoid tail makes it highly hydrophobic, and it diffuses freely in the hydrophobic core of the inner mitochondrial membrane. As a result, it shuttles electrons from Complexes I and II to Complex III. The redox cycle of UQ is shown in Figure 21.5, and the overall scheme is shown schematically in Figure 21.6. 

Cytochrome c, like UQ is a mobile electron carrier. It associates loosely with the inner mitochondrial membrane (in the intermembrane space on the cytosolic side of the inner membrane) to acquire electrons from the Fe-S-cyt C aggregate of Complex 111, and then it migrates along the membrane surface in the reduced state, carrying electrons to cytochrome c oxidase, the fourth complex of the electron transport chain. 

FIGURE 21.21 A model for the electron transport pathway in the mitochondrial inner membrane. UQ/UQH9 and cytochrome e are mobile electron carriers and function by transferring electrons between the complexes. The proton transport driven by Complexes I, III, and IV is indicated. 

The characteristic derivative-shaped feature at g 1.94 first observed in mitochondrial membranes has long been considered as the sole EPR fingerprint of iron-sulfur centers. The EPR spectrum exhibited by [4Fe-4S] centers generally reflects a ground state with S = I and is characterized by g values and a spectral shape similar to those displayed by [2Fe-2S] centers (Fig. 6c). Proteins containing [4Fe-4S] centers, which are sometimes called HIPIP, essentially act as electron carriers in the photoinduced cyclic electron transfer of purple bacteria (106), although they have also been discovered in nonphotosynthetic bacteria (107). Their EPR spectrum exhibits an axial shape that varies little from one protein to another with g// 2.11-2.14 and gi 2.03-2.04 (106-108), plus extra features indicative of some heterogeneous characteristics (Pig. 6d). 

Ubiquinone, known also as coenzyme Q, plays a crucial role as a respiratory chain electron carrier transport in inner mitochondrial membranes. It exerts this function through its reversible reduction to semiquinone or to fully hydrogenated ubiquinol, accepting two protons and two electrons. Because it is a small lipophilic molecule, it is freely diffusable within the inner mitochondrial membrane. Ubiquinones also act as important lipophilic endogenous antioxidants and have other functions of great importance for cellular metabolism. ... 

Now, we may consider in detail the mechanism of oxygen radical production by mitochondria. There are definite thermodynamic conditions, which regulate one-electron transfer from the electron carriers of mitochondrial respiratory chain to dioxygen these components must have the one-electron reduction potentials more negative than that of dioxygen Eq( 02 /02]) = —0.16 V. As the reduction potentials of components of respiratory chain are changed from 0.320 to +0.380 V, it is obvious that various sources of superoxide production may exist in mitochondria. As already noted earlier, the two main sources of superoxide are present in Complexes I and III of the respiratory chain in both of them, the role of ubiquinone seems to be dominant. Although superoxide may be formed by the one-electron oxidation of ubisemiquinone radical anion (Reaction (1)) [10,22] or even neutral semiquinone radical [9], the efficiency of these ways of superoxide formation in mitochondria is doubtful. 

Ubiquinones (coenzymes Q) Q9 and Qi0 are essential cofactors (electron carriers) in the mitochondrial electron transport chain. They play a key role shuttling electrons from NADH and succinate dehydrogenases to the cytochrome b-c1 complex in the inner mitochondrial membrane. Ubiquinones are lipid-soluble compounds containing a redox active quinoid ring and a tail of 50 (Qio) or 45 (Q9) carbon atoms (Figure 29.10). The predominant ubiquinone in humans is Qio while in rodents it is Q9. Ubiquinones are especially abundant in the mitochondrial respiratory chain where their concentration is about 100 times higher than that of other electron carriers. Ubihydroquinone Q10 is also found in LDL where it supposedly exhibits the antioxidant activity (see Chapter 23). 

There are two kinds of redox interactions, in which ubiquinones can manifest their antioxidant activity the reactions with quinone and hydroquinone forms. It is assumed that the ubiquinone-ubisemiquinone pair (Figure 29.10) is an electron carrier in mitochondrial respiratory chain. There are numerous studies [235] suggesting that superoxide is formed during the one-electron oxidation of ubisemiquinones (Reaction (25)). As this reaction is a reversible one, its direction depends on one-electron reduction potentials of semiquinone and dioxygen. 

It is noteworthy that except for the Rieske center in Complex III, Complexes I and 11 are home to all the iron-sulfur clusters in the mitochondrial electron transfer chain and consequently most of the iron-containing carriers in the entire sequence. Hibbs subsequently showed that CAM-injured cells lose a substantial portion of their total intracellular iron (Hibbs et al., 1984) [later studies specifically identified loss of mitochondrial iron (Wharton et al., 1988)] and Drapier and Hibbs (1986) showed that the activity of another iron-sulfur-containing enzyme, aconitase, is also lost. In early 1987 Hibbs reported that the cytostatic actions of CAMs requires the presence of only one component in culture medium, L-arginine (Hibbs et al., 1987b). Thus, the stage was set for the discovery of a unique reactive species that targets intracellular iron, produced by CAMs. 

A nonmitochondrial muscle diaphorase has also been described (Koizumi and Brown (1971), capable of forming NOMb in solutions containing nitrite and Mb, using methylene blue as a nonspecific electron carrier. NOMb formation by both the mitochondrial and mtnmitochondrial diaphorase enzyme systems requires the presence of reduced NADH. 

The basic mechanism underlying the toxicity of salicylate is the uncoupling of oxidative phosphorylation. For oxidative phosphorylation to take place, there is a requirement of a charge difference between the intermembrane space and the matrix of the mitochondria (Fig. 7.60). This is achieved when electrons move down the chain of multienzyme complexes and electron carriers (the electron transport chain), causing protons to move from the mitochondrial matrix to the intermembrane space. Consequently, a pH difference builds up, which is converted into an electrical potential across the membrane of approximately 200 mV over 8 nm. 

MPTP is a molecule, which is sufficiently lipophilic to cross the blood-brain barrier and enter the astrocyte cells. Once in these cells, it can be metabolized by monoamine oxidase B to MPDP and then MPP both of which are charged molecules. These metabolites are therefore not able to diffuse out of the astrocyte into the bloodstream and away from the brain. However, the structure of MPP allows it to be taken up by a carrier system and concentrated in dopaminergic neurones. In the neurone, it inhibits the mitochondrial electron transport chain leading to damage to the neurone. 

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