Mitochondria respiration

Fiorucci L, Monti A, Testai E, et al. 1988. In vitro effects of polyhalogenated hydrocarbons on liver mitochondria respiration and microsomal cytochrome p-450. Drug Chem Toxicol 11 387-403. 

Current estimates are that three protons move into the matrix through the ATP-synthase for each ATP that is synthesized. We see below that one additional proton enters the mitochondrion in connection with the uptake of ADP and Pi and export of ATP, giving a total of four protons per ATP. How does this stoichiometry relate to the P-to-O ratio When mitochondria respire and form ATP at a constant rate, protons must return to the matrix at a rate that just balances the proton efflux driven by the electron-transport reactions. Suppose that 10 protons are pumped out for each pair of electrons that traverse the respiratory chain from NADH to 02, and 4 protons move back in for each ATP molecule that is synthesized. Because the rates of proton efflux and influx must balance, 2.5 molecules of ATP (10/4) should be formed for each pair of electrons that go to 02. The P-to-O ratio thus is given by the ratio of the proton stoichiometries. If oxidation of succinate extrudes six protons per pair of electrons, the P-to-O ratio for this substrate is 6/4, or 1.5. These ratios agree with the measured P-to-O ratios for the two substrates. 

Oligomycin is an antibiotic that inhibits respiration in intact mitochondria. Respiration is not inhibited in uncoupled mitochondria, i.e., those mitochondria in which 02 consumption occurs but in which no ATP is synthesized. Thus, oligomycin does not block respiratory carriers, in contrast to inhibitors such as rotenone and cyanide. Instead, oligomycin blocks proton translocation through the F component to the F( component, through a specific interaction with a subunit of the membrane-associated F . The subscript o in the term F was originally used to indicate the oligomycin-sensitive" complex. 

Cytochrome oxidase catalyses electron transfer from cytochrome c to dioxygen, reducing the latter to water without release of intermediates. The maximal electron transfer activity may reach 400 (moles of cytochrome c oxidised per second per mole of cytochrome aa ) in optimal conditions at pH 7 and 25°C, both in situ and in detergent solution, although much lower activities are often encountered in the latter case (see Ref. 99). In mitochondria, respiration with natural substrates proceeds at much lower rates (cf.. Section 2.3). The kinetic capacity of cytochrome oxidase greatly exceeds demands for reasons not understood at present. 

Mingatto FE, Santos AC, Uyemura SA, Jordani MC, Curti C (1996) In vitro interaction of nonsteroidal anti-inflammatory drugs on oxidative phosphorylation of rat kidney mitochondria respiration and ATP synthesis. Arch Biochem Biophys 334(2) 303-308 Mingatto FE, Rodrigues T, Pigoso AA, Uyemura SA, Curti C, Santos AC (2002) The critical role of mitochondrial energetic impairment in the toxicity of nimesulide to hepatocytes. J Pharmacol Exp Ther 303 (2) 601-607... 

The rate of mitochondria respiration was measured with the aid of Clarke oxygen electrodes and LP-7 polarograph (Czechia). Mitochondria were ineubated in a medium containing 0.4 M sucrose, 20 mM HEPES-Tris buffer (pH 7.2), 5 mM KH PO, 4 mM MgClj, 5 mM EDTA and 0.1% BSA, 10 mM mlate + glutamate, pH 7.4. The rate of respiration was expressed in ng-atom 0/(mg protein min). 

BIOLOGICAL ACTIVITY (l-Adrenergic receptor mutant [6848] antiinflammatory [6713] as trypanocide, mitochondria respiration response [6849] trypanosoma brucei brucei inhibition [6780] pharmacological [6828] antimelanoma [6778]. 

It has been known for many years that the mitochondrion shows a respiration-linked transport of a number of ions. Of these, calcium has attracted the most attention since it depends on a specific transport system with high-affinity binding sites. The uptake of calcium usually also involves a permeant anion, but in the absence of this, protons are ejected as the electron transfer system operates. The result is either the accumulation of calcium salts in the mitochondrial matrix or an alkalinization of the interior of the mitochondrion. The transfer of calcium inwards stimulates oxygen utilization but provides an alternative to the oxidative phosphorylation of ADP618 ... 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eulcaiyotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessaiy for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphoiylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eulcaiyotes, the mitochondrion is the site of most energy-yielding... 

Mitochondria are present in all eukaryotic cells that use oxygen in respiration, but the number per cell and the form and size vary.1-4 Certain tiny trypanosomes have just one mitochondrion but some oocytes have as many as 3 x 105. Mammalian cells typically contain several hundred mitochondria and liver cells5 more than 1000. Mammalian sperm cells may contain 50-75 mitochondria,6 but in some organisms only one very large helical mitochondrion, formed by the fusion of many individual mitochondria, wraps around the base of the tail. Typical mitochondria appear to be about the size of cells of E. coli. However, study of ultrathin serial sections of a single yeast cell by electron microscopy has shown that, under some growth conditions, all of the mitochondria are interconnected.7... 

Calcium levels are believed to be controlled in part at least by the uptake and release of Ca2+ from mitochondria.172"174 The capacity of mitochondria for Ca2+ seems to be more than sufficient to allow the buffering of Ca2+ at low cytosol levels. Mitochondria take up Ca2+ by an energy-dependent process either by respiration or ATP hydrolysis. It is now agreed that Ca2+ enters in response to the negative-inside membrane potential developed across the inner membrane of the mitochondrion during respiration. The uptake of Ca2+ is compensated for by extrusion of two H+ from the matrix, and is mediated by a transport protein. Previous suggestions for a Ca2+-phosphate symport are now discounted. The possible alkalization of the mitochondrial matrix is normally prevented by the influx of H+ coupled to the influx of phosphate on the H - PCV symporter (Figure 10). This explains why uptake of Ca2+ is stimulated by phosphate. Other cations can also be taken up by the same mechanism. 

Therefore, as a mitochondrion membrane is broken, it somewhat disrupts communications between two conjugated reactions (respiration and phosphorylation). Hence, as expected, phosphorylation is completely terminated. This kinetic behavior of the system, both unclear and unusual at first glance, is quite logical, and is associated with the membrane origin of the ATP synthesis. 

Figure 7.1 The mitochondrion is found in all cells and contains many structures. This includes the cristae, where most ATP is produced in the final stage of cellular respiration. Being the site of ATP production, the mitochondrion is called the powerhouse of the cell.

The control of the respiration process and ATP synthesis shifts as the metabolic state of the mitochondria changes. In an isolated mitochondrion, control over the respiration process in state 4 is mainly due to the proton leak through the mitochondrial inner membrane. This type of control decreases from state 4 to state 3, while the control by the adenine nucleotide and the dicarboxylate carriers, cytochrome oxidase, increases. ATP utilizing reactions and transport activities also increase. Therefore, in state 3, most of the control is due to respiratory chain and substrate transport. 

Globally speaking, photosynthesis takes place in the chloroplast and respiration takes place in the mitochondrion. Both chloroplasts and mitochondria are organelles of eukaryotic cells. They look in many respects like cells within the cell and... 

Actively respiring fungal cells possess a distinct mitochondrion, which has been described as the power-house of the cell (Fig. 4.2). The enzymes of the tricarboxylic acid cycle (Kreb s cycle) are located in the matrix of the mitochondrion, while electron transport and oxidative phosphorylation occur in the mitochondrial inner membrane. The outer membrane contains enzymes involved in lipid biosynthesis. The mitochondrion is a semiindependent organelle as it possesses its own DNA and is capable of producing its own proteins on its own ribosomes, which are referred to as mitoribosomes. 

Krebs cycle A biochemical cycle in the second stage of cellular respiration involving eight steps that complete the metabolic breakdown of glucose molecules to carbon dioxide. Acetyl CoA is combined with oxaloac-etate to form citric acid. Citric acid is then converted into a number of other chemicals, and carbon dioxide is released. The process takes place within the mitochondrion. Also called citric acid cycle or tricarboxylic acid (TCA) cycle. Conceived and published by British scientist Sir Hans Adolf Krebs in 1957. 

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