)| PMID |
11050436 ( ) |
|---|---|
| Title | Mitochondria, oxygen free radicals, disease and ageing. |
| Abstract | Superoxide is generated by the mitochondrial respiratory chain. The transformation of this superoxide into hydrogen peroxide and, under certain conditions, then into hydroxyl radicals is important in diseases where respiratory chain function is abnormal or where superoxide dismutase function is altered, as in amyotrophic lateral sclerosis. In addition, these reactive oxygen species can influence the ageing process through mechanisms involving mutagenesis of mtDNA or increased rates of shortening of telomeric DNA. Sick Children, 555 University Ave., M5G 1X8, Toronto, Canada. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | 17 | MnSOD | MnSOD-depleted | |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | 6 | cytochrome b | |
| 7714 | NDUFS7 | NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) | 5 | PSST | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 4 | superoxide dismutase | |
| 118 | ACO2 | aconitase 2, mitochondrial | 3 | aconitase | |
| 19986 | CYCS | cytochrome c, somatic | 3 | cytochrome c | |
| 2244 | COQ7 | coenzyme Q7 homolog, ubiquinone (yeast) | 3 | clk 1 | |
| 1516 | CAT | catalase | 2 | catalase | |
| 7715 | NDUFS8 | NADH dehydrogenase (ubiquinone) Fe-S protein 8, 23kDa (NADH-coenzyme Q reductase) | 2 | TYKY | |
| 30862 | UQCR | ubiquinol-cytochrome c reductase, 6.4kDa subunit | 1 | ubiquinol cytochrome c reductase | |
| 7455 | MT-ND1 | mitochondrially encoded NADH dehydrogenase 1 | 1 | ND1 | |
| 7414 | MT-ATP6 | mitochondrially encoded ATP synthase 6 | 1 | ATP6 | |
| 7461 | MT-ND5 | mitochondrially encoded NADH dehydrogenase 5 | 1 | ND5 | |
| 7460 | MT-ND4L | mitochondrially encoded NADH dehydrogenase 4L | 1 | ND4L | |
| 12805 | XDH | xanthine dehydrogenase | 1 | xanthine oxidase | |
| 7456 | MT-ND2 | mitochondrially encoded NADH dehydrogenase 2 | 1 | ND2 | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 1 | bcl 2 | |
| 4553 | GPX1 | glutathione peroxidase 1 | 1 | GPX-1 | |
| 7458 | MT-ND3 | mitochondrially encoded NADH dehydrogenase 3 | 1 | ND3 | |
| 7415 | MT-ATP8 | mitochondrially encoded ATP synthase 8 | 1 | ATP8 | |
| 7462 | MT-ND6 | mitochondrially encoded NADH dehydrogenase 6 | 1 | ND6 | |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | 1 | cytochrome c oxidase | |
| 7459 | MT-ND4 | mitochondrially encoded NADH dehydrogenase 4 | 1 | ND4 | |
| 2579 | CYC1 | cytochrome c-1 | 1 | cytochrome c 1 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD-depleted | 1.9 | inhibitors on superoxide production in isolated whole mitochondria compared with MnSOD-depleted submitochondrial particles also suggests that there is a sidedness to |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | is likewise suggested by the presence of appreciable levels of MnSOD in the mitochondrial matrix and the comparatively low levels of |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | comparatively low levels of superoxide production by whole mitochondria containing MnSOD ( Ref 23 |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | For example damage to the cytosolic isoenzyme of aconitase evident after exposure to superoxide results in the release of |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | The damage to other systems such as mitochondrial aconitase complex I and succinate dehydrogenase which also have important functional |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | also have important functional iron-sulphur centres becomes very pronounced in MnSOD knockout mice where superoxide produced in the mitochondria is not |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | birth with the severe phenotypic changes evident in mice lacking MnSOD which suggests that either the mitochondria are more susceptible to |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | from patients with complex I deficiency displayed significant elevations of MnSOD sometimes two- to threefold whereas patients with defects in complex |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | symptoms (EI EI and CD were less likely to induce MnSOD above the basal levels normally seen in fibroblasts whereas patients |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | LD FILA which were usually fatal always had elevations of MnSOD ( 20 and 27 |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | increased superoxide production from complex I with no increase in MnSOD ( 26 |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | The correlation of increased levels of expression of MnSOD with a poor prognosis in complex I deficiency suggests that |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | deficiency suggests that responding to the increased superoxide by inducing MnSOD could itself be detrimental in the long term because of |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | radical were demonstrated in cell lines with increased induction of MnSOD ( 28 |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | to form increased amounts of superoxide (iv) iv induction of MnSOD (v) v increased formation of hydrogen peroxide from superoxide via |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | (v) v increased formation of hydrogen peroxide from superoxide via MnSOD or (vi) vi transformation of hydrogen peroxide to hydroxyl radicals |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | The overexpression of MnSOD in cultured rat glioma cells made those cells more sensitive |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | to damage by radiation and carcinogens 45 and 46 whereas MnSOD overexpression in mouse heart is protective against adriamycin-induced cardiotoxicity 47 |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | alternative scenario superoxide attacks enzymes (usually usually hydrolyases such as aconitase with 4Fe-4S centres releasing ferrous ions |
| 7715 | NDUFS8 | NADH dehydrogenase (ubiquinone) Fe-S protein 8, 23kDa (NADH-coenzyme Q reductase) | TYKY | 1.9 | are then passed to two 4Fe-4S centres in the 23-kDa TYKY subunit and a single 4Fe-4S centre in the 20-kDa PSST |
| 7714 | NDUFS7 | NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) | PSST | 1.9 | TYKY subunit and a single 4Fe-4S centre in the 20-kDa PSST subunit both of which are associated with the membrane-spanning segment |
| 7714 | NDUFS7 | NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) | PSST | 1.9 | in the matrix arm of the enzyme and one in PSST |
| 7714 | NDUFS7 | NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) | PSST | 1.9 | drawn with a single reduction site encompassing the 49-kDa and PSST subunits at the right-hand side of the complex |
| 7714 | NDUFS7 | NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) | PSST | 1.9 | 49-kDa subunit and rotenone inhibition of the complex at the PSST subunit are shown but it is possible to draw a |
| 7715 | NDUFS8 | NADH dehydrogenase (ubiquinone) Fe-S protein 8, 23kDa (NADH-coenzyme Q reductase) | TYKY | 1.9 | Boxes depicted in the TYKY and PSST subunits show the cubic arrangement of the 4Fe-4S |
| 7714 | NDUFS7 | NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase) | PSST | 1.9 | Boxes depicted in the TYKY and PSST subunits show the cubic arrangement of the 4Fe-4S centres with |
| 7455 | MT-ND1 | mitochondrially encoded NADH dehydrogenase 1 | ND1 | 0.9 | MtDNA genes include those for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( |
| 7456 | MT-ND2 | mitochondrially encoded NADH dehydrogenase 2 | ND2 | 0.9 | MtDNA genes include those for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( cyt |
| 7458 | MT-ND3 | mitochondrially encoded NADH dehydrogenase 3 | ND3 | 0.9 | MtDNA genes include those for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( cyt b |
| 7459 | MT-ND4 | mitochondrially encoded NADH dehydrogenase 4 | ND4 | 0.9 | genes include those for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( cyt b for |
| 7460 | MT-ND4L | mitochondrially encoded NADH dehydrogenase 4L | ND4L | 1.9 | include those for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( cyt b for complex |
| 7461 | MT-ND5 | mitochondrially encoded NADH dehydrogenase 5 | ND5 | 0.9 | those for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( cyt b for complex IV |
| 7462 | MT-ND6 | mitochondrially encoded NADH dehydrogenase 6 | ND6 | 0.9 | for complex I ( ND1 ND2 ND3 ND4 ND4L ND5 ND6 for complex III ( cyt b for complex IV ( |
| 7414 | MT-ATP6 | mitochondrially encoded ATP synthase 6 | ATP6 | 1.9 | IV ( COXI COXII COXIII and for complex V ( ATP6 ATP8 |
| 7415 | MT-ATP8 | mitochondrially encoded ATP synthase 8 | ATP8 | 1.9 | ( COXI COXII COXIII and for complex V ( ATP6 ATP8 |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | MnSOD | 1.9 | O 2 by CuZnSOD if in the matrix space by MnSOD |
| 4553 | GPX1 | glutathione peroxidase 1 | GPX-1 | 0.9 | peroxide in both compartments is achieved by glutathione peroxidase (GPX-1), GPX-1 which exists both in the cytosol and in the mitochondrial |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | the transformation of this superoxide into hydrogen peroxide and under certain conditions then into hydroxyl radicals is important in diseases where respiratory chain function is abnormal or where superoxide dismutase function is altered as in amyotrophic lateral sclerosis. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | ubiquinol cytochrome c oxidoreductase is responsible for taking reducing equivalents which are generated in complexes i and ii and contained in ubiquinol and transfer ring them through reactions with cytochrome b the rieske iron sulphur protein and cytochrome c 1 to the final electron acceptor cytochrome c . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | complex iii ubiquinol cytochrome c oxidoreductase is responsible for taking reducing equivalents which are generated in complexes i and ii and contained in ubiquinol and transfer ring them through reactions with cytochrome b the riesk |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | ble for taking reducing equivalents which are generated in complexes i and ii and contained in ubiquinol and transfer ring them through reactions with cytochrome b the rieske iron sulphur protein and cytochrome c 1 to the final electron acceptor cytochrome c . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | 1 to the final electron acceptor cytochrome c . |
| 2579 | CYC1 | cytochrome c-1 | cytochrome c 1 | 1.0 | ble for taking reducing equivalents which are generated in complexes i and ii and contained in ubiquinol and transfer ring them through reactions with cytochrome b the rieske iron sulphur protein and cytochrome c 1 to the final electron acceptor cytochrome c . |
| 30862 | UQCR | ubiquinol-cytochrome c reductase, 6.4kDa subunit | ubiquinol cytochrome c reductase | 1.0 | the q cycle mechanism proposed for the operation of the ubiquinol cytochrome c reductase operates as follows. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | iquinol donates one electron to the rieske iron sulphur protein a myxathiazol inhibitor site generating a semiquinone in proximity to the outer face of the inner membrane which then reduces the first cytochrome b haem b l . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | the second cytochrome b haem b h situated closer to the matrix side of the membrane accepts an electron from the first haem and reduces ubiquinone to form ubisemiquinone and subsequently with passage of another electron to |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | blocking electron passage out of cytochrome b h prevents the semiquinone at the q o site from donating its electron and so inhibition with antimycin produces a >tenfold increase in superoxide production from complex iii fig 3 . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | the mutations seen in cuznsod in als patients are odd in that they do not destroy superoxide dismutase activity even though they sometimes affect enzyme stability [ 5 6 and 29 ]. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | in transgenic mice bearing cuznsod mutations known to cause als in humans the protective bcl 2 protein when overexpressed transgenically can protect against neuronal death brought about by als mutations in experimental animals [ 37 and 38 ]. |
| 2244 | COQ7 | coenzyme Q7 homolog, ubiquinone (yeast) | clk 1 | 1.0 | one intriguing example of the link between the ros generating function of the respiratory chain and life span is that provided by the clk 1 protein. |
| 2244 | COQ7 | coenzyme Q7 homolog, ubiquinone (yeast) | clk 1 | 1.0 | the clk 1 protein is responsible for one of the final steps in ubiquinone synthesis so that defective activity results in low endogenous synthesis of ubiquinone for the mitochondrial respiratory chain. |
| 1516 | CAT | catalase | catalase | 1.0 | thus transgenic drosophila with increased expression of cuznsod did not show increased life span unless accompanied by increased expression of catalase to remove the hydrogen peroxide. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | in mammals increased life span by transgenic modulation of levels of superoxide dismutase has not been observed [ 42 and 43 ]. |
| 2244 | COQ7 | coenzyme Q7 homolog, ubiquinone (yeast) | clk 1 | 1.0 | interference with ubiquinone synthesis in some organisms as demonstrated by the c. elegans clk 1 mutants would be expected to cause a reduction in ubisemiquinone levels a reduction in mitochondrial superoxide production and a subsequent deceleration of shortening and increase in life span[ 40 ]. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | oxygen is initially converted to superoxide o 2 _amp_#x2212; either by xanthine oxidase respiratory chain complexes i and iii or other cellular enzymes. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | the superoxide is converted to hydrogen peroxide h 2 o 2 by superoxide dismutase. |
| 1516 | CAT | catalase | catalase | 1.0 | hydrogen peroxide is converted to water by either catalase or glutathione peroxidase. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | this then promptly reduces the b l haem of cytochrome b . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | the b h haem of cytochrome b then reduces ubiquinone q to produce another ubisemiquinone. |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | complex i nadh ubiquinone oxidoreductase complex iii ubiquinol cytochrome c oxidoreductase complex iv cytochrome c oxidase and complex v h + translocating atp synthetase are shown. |