Effects of peroxisomal catalase inhibition on mitochondrial function.
Peroxisomes produce hydrogen peroxide as a metabolic by-product of their many oxidase enzymes, but contain catalase that breaks down hydrogen peroxide in order to maintain the organelle’s oxidative balance. It has been previously demonstrated that, as cells age, catalase is increasingly absent from...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-04-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00108/full |
| _version_ | 1818151507025985536 |
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| author | Paul eWalton |
| author_facet | Paul eWalton |
| author_sort | Paul eWalton |
| collection | DOAJ |
| description | Peroxisomes produce hydrogen peroxide as a metabolic by-product of their many oxidase enzymes, but contain catalase that breaks down hydrogen peroxide in order to maintain the organelle’s oxidative balance. It has been previously demonstrated that, as cells age, catalase is increasingly absent from the peroxisome, and resides instead as an unimported tetrameric molecule in the cell cytosol; an alteration that is coincident with increased cellular hydrogen peroxide levels. As this process begins in middle-passage cells, we sought to determine whether peroxisomal hydrogen peroxide could contribute to the oxidative damage observed in mitochondria in late-passage cells. Early-passage human fibroblasts (Hs27) treated with aminotriazole (3-AT), an irreversible catalase inhibitor, demonstrated decreased catalase activity, increased levels of cellular hydrogen peroxide, protein carbonyls, and peroxisomal numbers. This treatment increased mitochondrial ROS levels, and decreased the mitochondrial aconitase activity by approximately 85% within 24 hours. In addition, mitochondria from 3-AT treated cells show a decrease in inner membrane potential. These results demonstrate that peroxisome-derived oxidative imbalance may rapidly impair mitochondrial function, and considering that peroxisomal oxidative imbalance begins to occur in middle-passage cells, supports the hypothesis that peroxisomal oxidant release occurs upstream of, and contributes to, the mitochondrial damage observed in aging cells. |
| first_indexed | 2024-12-11T13:39:55Z |
| format | Article |
| id | doaj.art-ecccb2524e134888843aba4514905dd5 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-11T13:39:55Z |
| publishDate | 2012-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ecccb2524e134888843aba4514905dd52022-12-22T01:04:50ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-04-01310.3389/fphys.2012.0010823357Effects of peroxisomal catalase inhibition on mitochondrial function.Paul eWalton0University of Western OntarioPeroxisomes produce hydrogen peroxide as a metabolic by-product of their many oxidase enzymes, but contain catalase that breaks down hydrogen peroxide in order to maintain the organelle’s oxidative balance. It has been previously demonstrated that, as cells age, catalase is increasingly absent from the peroxisome, and resides instead as an unimported tetrameric molecule in the cell cytosol; an alteration that is coincident with increased cellular hydrogen peroxide levels. As this process begins in middle-passage cells, we sought to determine whether peroxisomal hydrogen peroxide could contribute to the oxidative damage observed in mitochondria in late-passage cells. Early-passage human fibroblasts (Hs27) treated with aminotriazole (3-AT), an irreversible catalase inhibitor, demonstrated decreased catalase activity, increased levels of cellular hydrogen peroxide, protein carbonyls, and peroxisomal numbers. This treatment increased mitochondrial ROS levels, and decreased the mitochondrial aconitase activity by approximately 85% within 24 hours. In addition, mitochondria from 3-AT treated cells show a decrease in inner membrane potential. These results demonstrate that peroxisome-derived oxidative imbalance may rapidly impair mitochondrial function, and considering that peroxisomal oxidative imbalance begins to occur in middle-passage cells, supports the hypothesis that peroxisomal oxidant release occurs upstream of, and contributes to, the mitochondrial damage observed in aging cells.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00108/fullAgingCatalaseHydrogen PeroxideMitochondriasenescenceperoxisome |
| spellingShingle | Paul eWalton Effects of peroxisomal catalase inhibition on mitochondrial function. Frontiers in Physiology Aging Catalase Hydrogen Peroxide Mitochondria senescence peroxisome |
| title | Effects of peroxisomal catalase inhibition on mitochondrial function. |
| title_full | Effects of peroxisomal catalase inhibition on mitochondrial function. |
| title_fullStr | Effects of peroxisomal catalase inhibition on mitochondrial function. |
| title_full_unstemmed | Effects of peroxisomal catalase inhibition on mitochondrial function. |
| title_short | Effects of peroxisomal catalase inhibition on mitochondrial function. |
| title_sort | effects of peroxisomal catalase inhibition on mitochondrial function |
| topic | Aging Catalase Hydrogen Peroxide Mitochondria senescence peroxisome |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00108/full |
| work_keys_str_mv | AT paulewalton effectsofperoxisomalcatalaseinhibitiononmitochondrialfunction |