Biophysics of Mitochondria by Nikolai Vekshin

Author:Nikolai Vekshin
Language: eng
Format: epub, pdf
ISBN: 9783030338534
Publisher: Springer International Publishing

6.3.1 Conclusion

The resonant energy transfer from tryptophan residues to bound NADH in MCs has been confirmed. On average, only one tryptophan residue is an energy donor for one NADH acceptor molecule. The increase in the fluorescence of mitochondrial proteins, observed in hypotonic medium and in response to the addition of calcium, is due to the oxidation of NADH, but not to the conformational changes of proteins.

6.4 Loss of Flavin from Enzyme

When complex I damaged, it lost the NADH: ubiquinone reductase activity [50–53]. High probability of damage is due to several reasons. First, this complex in the respiratory chain is the first key. Secondly, it is extremely large. Thirdly, it contains 6–8 labile iron-sulfur clusters and a weakly bound flavin. Fourth, its functioning is associated with proton transfer and ATP synthesis. Therefore, the slightest damage leads to an avalanche of disorders, to mitochondrial diseases [54–58].

The peripheral flavoprotein fragment of complex I consist of three main subunits: 51, 24, and 9 kDa. The heavy 51-kDa subunit contains flavin (FMN or, possibly, FAD) and is responsible for the binding of NADH [52, 53]. The fragment catalyzes the rapid rotenone-insensitive oxidation of NADH by artificial acceptors, including ferricyanide. Neither ubiquinone nor flavin participates in the NADH: ferricyanide reductase reaction [59–61]. When the fragment is divided into individual components, flavin goes into solution in the form of FMN, and the obtained fractions (51 kDa and 24 + 9 kDa) become catalytically inactive [62].

Complex I play an important role in the formation of superoxide [63, 64] and lipid peroxidation [65], leading to membrane damage and, as a result, to dysfunction. Disturbances of complex I is a characteristic of aging [56]. In MCs of aging organisms, lipid peroxides accumulates, therefore, proteins and DNA are damaged. Neuromuscular systems are involved in the pathological process, requiring a lot of energy. If any damage appears at the level of complex I, the ATP ceases to be produced there [57, 66]. That is why encephalomyopathy occurs. Damage of complex I in the brain and muscle cells plays a crucial role in the development of Parkinson’s disease and others disorders [55, 66–73].

Disruptions in the operation of complex I may occur under the action of various poisons and aggressive chemical substances. These include rotenoids, antibiotics, pesticides, barbiturates, etc. [74]. Such substances block the active centers of the enzyme or violate its conformation. There is evidence of inhibition of complex I by non-ionic detergents like Triton X-100 [75, 76].

The cause of a number of mitochondrial pathologies may be a loss of flavin from the active center of the enzyme. Flavin in the enzyme is the “weak link”. The loss of flavin (in the form of FMN or riboflavin) can occur as its release into aqueous phase due to conformational rearrangements of the enzyme. Although flavin is located inside the protein globule, it can easily be lost, because bound not firmly. A loss of flavin during the isolation and purification of the enzyme is well-known [50, 51, 61]. The purified enzyme usually has a low NADH: ubiquinone reductase activity, but a high NADH: ferricyanide reductase activity [50–53].

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