Electron transport mitochondrial, components

Much progress has been made in understanding the different mechanisms that can cause mitochondrial dysfunction, such as (i) uncoupling of electron transport from ATP synthesis by undermining integrity of inner membrane (ii) direct inhibition of electron transport system components (iii) opening of the mitochondrial permeability transition pore leading to irreversible collapse of the transmembrane potential and release of pro-apoptotic factors (iv) inhibition of the... 

Zhang Y, Marcillat O, Giulivi C, Emster L, Davies KJ. 1990. The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem 265 16330-16336. 

The mitochondrial inner membrane (Fig. 7) contains proteins that act in concert to catalyze NADH and FADH2 oxidation by molecular oxygen. [See reactions (2) and (3) above.] These reactions are carried out in many small steps by proteins that are integral to the membrane and that undergo oxidation-reduction. These proteins make up what is called the mitochondrial electron transport chain. Components of the chain include iron proteins (cytochromes and iron-sulfur proteins), flavoproteins (proteins that contain flavin), copper, and quinone binding proteins. 

It is not inconceivable that such permeability effects are a result of an initial direct effect of herbicide binding to ATPase or an electron transport chain component and/or a protonophore action. However, most, if not all, the herbicides discussed in this section can be classed as multisite inhibitors as evidenced by their inclusion in previous chapters, particularly Chapter 1, and elsewhere in this chapter. Such a membrane partitioning would not be specific to the inner mitochondrial membrane but would occur in other... 

FIGURE 21.3 % J and % values for the components of the mitochondrial electron transport chain. Values indicated are consensus values for animal mitochondria. Black bars represent %r red bars,. ... 

It is important that mitochondrial oxygen radical production depends on the type of mitochondria. Recently, Michelakis et al. [78] demonstrated that hypoxia and the proximal inhibitors of electron transport chain (rotenone and antimycin) decreased mitochondrial oxygen radical production by pulmonary arteries and enhanced it in renal arteries. This difference is probably explained by a lower expression of the proximal components of electron transport chain and a greater expression of mitochondrial MnSOD in pulmonary arteries compared to renal arteries. 

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. 

Mitochondrial diseases are often expressed as neuropathies and myopathies because brain and muscle are highly dependent on oxidative phosphorylation. Mitochondrial genes code for some of the components of the electron transport chain and oxidative phosphorylation, as well as some mitochondrial tRNA molecules. 

A polyprenylated benzoquinone derivative that is a key component in mitochondrial electron transport, and the... 

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. 

The drug interferes with the mitochondrial electron transport chain. It seems that this is due to a high affinity of the drug for lipids such as cardiolipin, a component of the mitochondrial inner membrane. It therefore accumulates there. 

Correct answer = D. Thirteen of the approximately 100 polypeptides required for oxidative phosphorylation are coded for by mitochondrial DNA, including the electron transport components cytochrome c and coenzyme Q. Oxygen directly oxidizes cytochrome oxidase. Succinate dehydrogenase directly reduces FAD. Cyanide inhibits electron flow, proton pumping, and ATP synthesis. 

A second group of electron carriers in mitochondrial membranes are the iron-sulfur [Fe-S] clusters which are also bound to proteins. Iron-sulfur proteins release Fe3+ or Fe2+ plus H2S when acidified. The "inorganic clusters" bound into the proteins have characteristic compositions such as Fe2S2 and Fe4S4. The sulfur atoms of the clusters can be regarded as sulfide ions bound to the iron ions. The iron atoms are also attached to other sulfur atoms from cysteine side chains from the proteins. The Fe-S proteins are often tightly associated with other components of the electron transport chain. For example, the flavoproteins Flavin 1, Flavin 2, and Flavin 3 shown in Fig. 10-5 all contain Fe-S clusters as does the Q-cytochrome b complex. All of these Fe-S clusters seem to be one-electron carriers. 

A mutation in any of the 13 protein subunits, the 22 tRNAs, or the two rRNAs whose genes are carried in mitochondrial DNA may possibly cause disease. The 13 protein subunits are all involved in electron transport or oxidative phosphorylation. The syndromes resulting from mutations in mtDNA frequently affect oxidative phosphorylation (OXPHOS) causing what are often called "OXPHOS diseases."3-6 Mitochondrial oxidative phosphorylation also depends upon 100 proteins encoded in the nucleus. Therefore, OXPHOS diseases may result from defects in either mitochondrial or nuclear genes. The former are distinguished by the fact that they are inherited almost exclusively maternally. Most mitochondrial diseases are rare. However, mtDNA is subject to rapid mutation, and it is possible that accumulating mutants in mtDNA may be an important component of aging.h k... 

Figure 18-19 The ammonia oxidation system of the bacterium Nitrosomonas. Oxidation of ammonium ion (as free NH3) according to Eq. 18-17 is catalyzed hy two enzymes. The location of ammonia monooxygenase (step a) is uncertain but hydroxylamine oxidoreductase (step b) is periplas-mic. The membrane components resemble complexes I, III, and IV of the mitochondrial respiratory chain (Fig. 18-5) and are assumed to have similar proton pumps. Solid green lines trace the flow of electrons in the energy-producing reactions. This includes flow of electrons to the ammonia monoxygenase. Complexes HI and IV pump protons out but complex I catalyzes reverse electron transport for a fraction of the electrons from hydroxylamine oxidoreductase to NAD+. Modified from Blaut and Gottschalk.315...

The discussion to this point has focused on the isolation of intact mitochondria. By various chemical and physical treatments, mitochondria may be separated into their four components. This allows biochemists to study the biological functions of each component. For example, by measuring enzyme activities in each fraction, one can assign the presence of a particular enzyme to a specific region of the mitochondria. Studies of mitochondrial subfractions have resulted in a distribution analysis of enzyme activities in the four locations (Table E10.1). This type of study is often referred to as an enzyme profile or enzyme activity pattern and the enzyme may be considered a marker enzyme. For example, cytochrome oxidase, which is involved in electron transport, is a marker enzyme for the inner membrane. 

A certain component at this location must be essential for mediating the electron transport and would appear to be highly sensitive to the 4-hydroxyquinolines. This component must be a very specific chemotherapeutic target in eimeria species, since the 4-hydroxyquinolines have no effect on chicken liver and mammalian mitochondrial respiration and no activity against any parasites other than eimeria. 

ATP synthase is located in the inner mitochondrial membrane. It consists of two major components, F, ATPase [seen as spheres under the electron microscope and with a subunit structure of (aP ySe] attached to component F0 (coupling factor 0) which is a proton channel spanning this membrane. Hence, ATP synthase is also known as F0F, ATPase. In mitochondria, this complete complex uses the energy released by electron transport to drive ATP synthesis but, in isolation, F ATPase hydrolyzes ATP. During ATP hydrolysis, and presumably also during ATP synthesis, subunit y of F, ATPase rotates relative to (aP)3 and is the smallest rotatory engine known in nature. 

In eukaryotes, electron transport and oxidative phosphorylation occur in the inner membrane of mitochondria. These processes re-oxidize the NADH and FADH2 that arise from the citric acid cycle (located in the mitochondrial matrix Topic L2), glycolysis (located in the cytoplasm Topic J3) and fatty acid oxidation (located in the mitochondrial matrix Topic K2) and trap the energy released as ATP. Oxidative phosphorylation is by far the major source of ATP in the cell. In prokaryotes, the components of electron transport and oxidative phosphorylation are located in the plasma membrane (see Topic Al). 

In the photosynthetic and mitochondrial membranes the components of the transmembrane electron transport chain are not linked with covalent bonds, but fixed in a protein matrix. An example of such an arrangement of the electron transport chain in an artificial system can be found in papers by Tabushi et al. [244, 245], which deal with the dark electron transfer across the lipid membranes containing the dimers of cytochrome c3 from Desulfovibrio vulgaris. The dimer size is about 60 A, i.e. it somewhat exceeds the membrane thickness. This enables electron to move across the membrane via the cytochrome along the chain of hem fragments embedded in the protein. However, the characteristic time of the transmembrane electron transfer by this method is rather long (about 10 s). 

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