FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2242941828> ?p ?o ?g. }

• W2242941828 abstract "Human mitochondria contain a circular genome called mitochondrial DNA (mtDNA). It encodes subunits of the respiratory chain enzymes involved in energy conservation in oxidative phosphorylation and the necessary RNA needed for their expression. Errors in these genes have been shown to cause diseases, called mitochondrial diseases, which mainly affect tissues with high energydemand, such as brain, heart, and skeletal muscle, or to lead to the production of harmful by-products in the form of reactive oxygen species (ROS) during cellular respiration. ROS damage lipids, proteins, and DNA, especially mtDNA. Accumulation of mtDNA mutations has also been associated with aging. Mitochondrial complex I is located in the inner mitochondrial membrane and catalyzes NADHubiquinone oxidoreduction coupled to the translocation of four protons from the inside of the mitochondrion to the intermembranous space. Bacteria contain a homologous but simpler enzyme, NDH-1, with the same catalytic mechanism and which is therefore considered the catalytical core of mitochondrial complex I. Seven of the conserved membranous subunits in complex I are encoded in the mtDNA and are targets for mutations causing mitochondrial diseases, like MELAS syndrome or Leber hereditary optic neuropathy (LHON). We used Paracoccus denitrificans and Escherichia coli NDH-1 enzymes to reveal the role of selected conserved charged residues and MELAS or LHON amino acid substitutions in enzyme catalysis. The growth phenotypes and NDH-1-dependent activities in mutant bacterial membranes were characterized, in addition to the sensitivity to selected complex I inhibitors. In order to enable ROS production measurements in the bacterial model of human mitochondrial diseases, we evaluated the reliability of two superoxide detecting probes, lucigenin and coelenterazine. Elimination of the acidic residue in ND1 (position E228) previously found to cause MELAS, was found detrimental for NDH-1 assembly and activity. Also, elimination of the acidic residue at position E36 in ND4L resulted in an inactive enzyme. ND1-E216A, ND4L-E72Q and -E36Q/I39D/ A69D/E72Q substitutions decreased NDH-1 activity somewhat (normal activity in the last mutant), but displayed a negative growth phenotype under NDH-1 dependent conditions, suggestive of impaired energy conservation in these mutants. ND1-Y229, whose substitution causes MELAS, charged residues in loop five of ND1, and ND1-E157, whose substitution causes LHON, were also found important for the enzyme activity. Coelenterazine was found a reliable probe for quantitative superoxide production measurement in mitochondrial or bacterial membranes, and its sensitivity is not affected by the reduction level of the respiratory chain. Therefore, coelenterazine is suitable for quantitative superoxide production measurements." @default.
• W2242941828 created "2016-06-24" @default.
• W2242941828 creator A5002743390 @default.
• W2242941828 date "2006-01-01" @default.
• W2242941828 modified "2023-09-26" @default.
• W2242941828 title "Membranous core domain of Complex I and mitochondrial disease modeling" @default.
• W2242941828 cites W11949998 @default.
• W2242941828 cites W130095455 @default.
• W2242941828 cites W140926176 @default.
• W2242941828 cites W1440399798 @default.
• W2242941828 cites W1479788934 @default.
• W2242941828 cites W1484668578 @default.
• W2242941828 cites W1487169814 @default.
• W2242941828 cites W1505971231 @default.
• W2242941828 cites W1508115748 @default.
• W2242941828 cites W1510479518 @default.
• W2242941828 cites W1526469700 @default.
• W2242941828 cites W1532568205 @default.
• W2242941828 cites W1539549165 @default.
• W2242941828 cites W1551036491 @default.
• W2242941828 cites W1554459256 @default.
• W2242941828 cites W1556704697 @default.
• W2242941828 cites W1563180393 @default.
• W2242941828 cites W1565276006 @default.
• W2242941828 cites W1570597278 @default.
• W2242941828 cites W1576127641 @default.
• W2242941828 cites W1579208223 @default.
• W2242941828 cites W1585674762 @default.
• W2242941828 cites W1587218958 @default.
• W2242941828 cites W1592690611 @default.
• W2242941828 cites W1597487419 @default.
• W2242941828 cites W1602460334 @default.
• W2242941828 cites W163123111 @default.
• W2242941828 cites W1711526575 @default.
• W2242941828 cites W1752049494 @default.
• W2242941828 cites W1765516395 @default.
• W2242941828 cites W1775749144 @default.
• W2242941828 cites W1790985176 @default.
• W2242941828 cites W1804824036 @default.
• W2242941828 cites W1830842445 @default.
• W2242941828 cites W1831545473 @default.
• W2242941828 cites W1851154662 @default.
• W2242941828 cites W1877954338 @default.
• W2242941828 cites W1896713748 @default.
• W2242941828 cites W1923427359 @default.
• W2242941828 cites W1925814110 @default.
• W2242941828 cites W1940436875 @default.
• W2242941828 cites W1950005998 @default.
• W2242941828 cites W1963825697 @default.
• W2242941828 cites W1964126982 @default.
• W2242941828 cites W1965352756 @default.
• W2242941828 cites W1965662719 @default.
• W2242941828 cites W1966276039 @default.
• W2242941828 cites W1966571906 @default.
• W2242941828 cites W1966691625 @default.
• W2242941828 cites W1967678996 @default.
• W2242941828 cites W1967750933 @default.
• W2242941828 cites W1968219551 @default.
• W2242941828 cites W1968229549 @default.
• W2242941828 cites W1968315028 @default.
• W2242941828 cites W1968790281 @default.
• W2242941828 cites W1968940507 @default.
• W2242941828 cites W1968952472 @default.
• W2242941828 cites W1970143646 @default.
• W2242941828 cites W1970204920 @default.
• W2242941828 cites W1971221919 @default.
• W2242941828 cites W1972066943 @default.
• W2242941828 cites W1973211255 @default.
• W2242941828 cites W1973255798 @default.
• W2242941828 cites W1973701259 @default.
• W2242941828 cites W1975085160 @default.
• W2242941828 cites W1975541574 @default.
• W2242941828 cites W1976210582 @default.
• W2242941828 cites W1976314697 @default.
• W2242941828 cites W1976798586 @default.
• W2242941828 cites W1977174816 @default.
• W2242941828 cites W1977267670 @default.
• W2242941828 cites W1980226438 @default.
• W2242941828 cites W1980681204 @default.
• W2242941828 cites W1981613679 @default.
• W2242941828 cites W1981628967 @default.
• W2242941828 cites W1983034428 @default.
• W2242941828 cites W1983487087 @default.
• W2242941828 cites W1983737836 @default.
• W2242941828 cites W1983857347 @default.
• W2242941828 cites W1983918667 @default.
• W2242941828 cites W1985586629 @default.
• W2242941828 cites W1986003680 @default.
• W2242941828 cites W1986146756 @default.
• W2242941828 cites W1986956461 @default.
• W2242941828 cites W1988930583 @default.
• W2242941828 cites W1989114406 @default.
• W2242941828 cites W1989918507 @default.
• W2242941828 cites W1990082687 @default.
• W2242941828 cites W1991280425 @default.
• W2242941828 cites W1991316406 @default.
• W2242941828 cites W1994165455 @default.
• W2242941828 cites W1994838479 @default.
• W2242941828 cites W1995746334 @default.
• W2242941828 cites W1995925875 @default.

• next