Cytochromes in mitochondria

For n-type cytochromes in mitochondria, the sixth position is not bound to an amino acid but rather interacts with 02, Cu, or other ligands. 

Blausaure, prussic acid. Used in WWI only by France. Clear colourless liquid, odour of bitter almonds. Bp 25°C, mp -13.4°C vapour pressure at 15°C 500 mmHg. Lethal concentration 120-150 mg/m3 (1 h) 200 mg/m3 (10 min) figures vary with source < 30 mg/m3 said to be safe eliminated rapidly. Blocks cytochromes in mitochondria rapid collapse after a short period of hyperpnoea, dizziness and headache. CNS damage possible in some who recover from acute effects. 

The presence of a few type b cytochromes in mitochondria other than those in the respiratory chain has been reported. These are cytochrome... 

Cytochromes in Mitochondria. The majority of cytochromes occur entirely in mitochondria, where they are associated with large amounts of lipid. An intimate association exists between the cytochromes and succinic dehydrogenase to form succinoxidase, which retains the ability to oxidize succinate after all other oxidative reactions have been washed out of the particles. The activity of the succinoxidase system is sensitive to many environmental factors, which apparently influence the physical state of the particles. When mitochondria are exposed to distilled water, for example, cytochrome c is lost. Exogenous cytochrome c is used much less efficiently than particle-bound cytochrome. It is concluded from observations of this sort that the individual components, succinic dehydrogenase, cytochrome c, cytochrome a, and cytochrome oxidase, together with any other factors that may be involved, are fixed in position to react rapidly with each other, and do not depend on diffusion. 

Rieske proteins are constituents of the be complexes that are hydro-quinone-oxidizing multisubunit membrane proteins. All be complexes, that is, bci complexes in mitochondria and bacteria, b f complexes in chloroplasts, and corresponding complexes in menaquinone-oxidizing bacteria, contain three subunits cytochrome b (cytochrome 6e in b f complexes), cytochrome Ci (cytochrome f in b(,f complexes), and the Rieske iron sulfur protein. Cytochrome 6 is a membrane protein, whereas the Rieske protein, cytochrome Ci, and cytochrome f consist of water-soluble catalytic domains that are bound to cytochrome b through a membrane anchor. In Rieske proteins, the membrane anchor can be identified as an N-terminal hydrophobic sequence (13). 

The group of the be complexes comprises bci complexes in mitochondria and bacteria and bef complexes in chloroplasts. These complexes are multisubunit membrane proteins containing four redox centers in three subunits cytochrome b (cytochrome be in bef complexes) comprising two heme b centers in a transmembrane arrangement, cyto-... 

A decade after the discovery of the Rieske protein in mitochondria (90), a similar FeS protein was identified in spinach chloroplasts (91) on the basis of its unique EPR spectrum and its unusually high reduction potential. In 1981, the Rieske protein was shown to be present in purified cytochrome Sg/complex from spinach (92) and cyanobacteria (93). In addition to the discovery in oxygenic photosynthesis, Rieske centers have been detected in both single-RC photosynthetic systems [2] (e.g., R. sphaeroides (94), Chloroflexus (95)) and [1] (Chlo-robium limicola (96, 97), H. chlorum (98)). They form the subject of a review in this volume. 

Mechanistic studies have shown that TBT and certain other forms of trialkyltin have two distinct modes of toxic action in vertebrates. On the one hand they act as inhibitors of oxidative phosphorylation in mitochondria (Aldridge and Street 1964). Inhibition is associated with repression of ATP synthesis, disturbance of ion transport across the mitochondrial membrane, and swelling of the membrane. Oxidative phosphorylation is a vital process in animals and plants, and so trialkyltin compounds act as wide-ranging biocides. Another mode of action involves the inhibition of forms of cytochrome P450, which was referred to earlier in connection with metabolism. This has been demonstrated in mammals, aquatic invertebrates and fish (Morcillo et al. 2004, Oberdorster 2002). TBTO has been shown to inhibit P450 activity in cells from various tissues of mammals, including liver, kidney, and small intestine mucosa, both in vivo and in vitro (Rosenberg and Drummond 1983, Environmental Health Criteria 116). 

H)2-D3 is a weak agonist and must be modified by hydroxylation at position Cj for full biologic activity. This is accomplished in mitochondria of the renal proximal convoluted tubule by a three-component monooxygenase reaction that requires NADPFl, Mg, molecular oxygen, and at least three enzymes (1) a flavoprotein, renal ferredoxin reductase (2) an iron sulfur protein, renal ferredoxin and (3) cytochrome P450. This system produces l,25(OH)2-D3, which is the most potent namrally occurring metabolite of vitamin D. 

The above describes the major pathway of proteins destined for the mitochondrial matrix. However, certain proteins insert into the outer mitochoiidrial membrane facilitated by the TOM complex. Others stop in the intermembrane space, and some insert into the inner membrane. Yet others proceed into the matrix and then return to the inner membrane or intermembrane space. A number of proteins contain two signaling sequences—one to enter the mitochondrial matrix and the other to mediate subsequent relocation (eg, into the inner membrane). Certain mitochondrial proteins do not contain presequences (eg, cytochrome Cy which locates in the inter membrane space), and others contain internal presequences. Overall, proteins employ a variety of mechanisms and routes to attain their final destinations in mitochondria. 

Chance B, Schoener B. 1965. High and low energy states of cytochromes. I. In mitochondria. JBiol Chem 241 4567-4573. 

The cytochromes are another group of haem proteins found in all aerobic forms of life. Cytochromes are electron carriers involving a Fe(ii)/Fe(m) redox system. They are a crucial part of the electron transfer reactions in mitochondria, in aspects of the nitrogen cycle, and in enzymic processes associated with photosynthesis. 

The functions of mtNOS in mitochondria have been studied (see Chapter 23). Ghafourifar et al. [177] found that the calcium-induced stimulation of mtNOS caused the release of cytochrome c from mitochondria and induced apoptosis. On the other hand, the same group of authors [178] showed that the production of NO by mtNOS and superoxide in mitochondria resulted in the formation of peroxynitrite and stimulated calcium release, indicating the existence of a feedback loop which prevents calcium overload in mitochondria. 

Controversial results of oxygen radical detection in mitochondria have been described in the literature. Owing to experimental difficulties many authors were obliged to work with sub-mitochondrial particles instead of the whole mitochondria. However, it is quite possible that oxygen radical production by submitochondrial particles may be artificially enhanced due to exposure to oxygen. On the other hand, some analytical methods of superoxide detection such as cytochrome c reduction cannot be used due to the direct reduction of cytochrome by mitochondrial components. 

As a rule, oxygen radical overproduction in mitochondria is accompanied by peroxidation of mitochondrial lipids, glutathione depletion, and an increase in other parameters of oxidative stress. Thus, the enhancement of superoxide production in bovine heart submitochondrial particles by antimycin resulted in a decrease in the activity of cytochrome c oxidase through the peroxidation of cardiolipin [45]. Iron overload also induced lipid peroxidation and a decrease in mitochondrial membrane potential in rat liver mitochondria [46]. Sensi et al. [47] demonstrated that zinc influx induced mitochondrial superoxide production in postsynaptic neurons. 

The administration of Qio or quercetin to rats protected against endotoxin-induced shock in rat brain [252]. It was found that the pretreatment with these antioxidants diminished the shock-induced increase in brain MDA and nitric oxide levels. Interesting data have been obtained by Yamamura et al. [253] who showed that ubiquinone Qi0 is able to play a double role in mitochondria. It was found that on the one hand, Q10 enhanced the release of hydrogen peroxide from antimycin A- or calcium-treated mitochondria, but on the other hand, it inhibited mitochondrial lipid peroxidation. It was proposed that Q10 acts as a prooxidant participating in redox signaling and as an antioxidant suppressing permeability transition and cytochrome c release. 

Several different changes in mitochondria occur during apoptosis. These include a change in membrane potential (usually depolarization), increased production of reactive oxygen species, potassium channel activation, calcium ion uptake, increased membrane permeability and release of cytochrome c and apoptosis inducing factor (AIF) [25]. Increased permeability of the mitochondrial membranes is a pivotal event in apoptosis and appears to result from the formation of pores in the membrane the proteins that form such permeability transition pores (PTP) may include a voltage-dependent anion channel (VDAC), the adenine nucleotide translocator, cyclophilin D, the peripheral benzodiazepine receptor, hexokinase and... 

Darios, F., et ah. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet, 2003, 12(5), 517-26. 

Nomura et al. (2000) showed that hypoglycaemia-induced apoptosis of basophile leukemia ceUs involves the generation of cardiolipin hydroperoxide and the subsequent release of cytochrome c from mitochondria. (Nomura et al., 2000). The gaieration of cardiolipin hydroperoxide occurred in mitochondria of basophile leukaemia cells which had been induced to undergo apoptosis by exposure to hypoglycaemia with... 

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