Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome
© 2019 Wiley Periodicals, Inc. Mutations in the human SBDS gene is the most common cause of Shwachman-Diamond syndrome (SDS). The SBDS protein participates in ribosome biogenesis; however, effects beyond reduced translation efficiency are thought to be involved in SDS progression. Impaired mitochond...
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th-mahidol.501112020-01-27T14:40:47Z Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome Laran T. Jensen The Phyu Ayushi Jain Chonlada Kaewwanna Amornrat Naranuntarat Jensen Mahidol University Biochemistry, Genetics and Molecular Biology © 2019 Wiley Periodicals, Inc. Mutations in the human SBDS gene is the most common cause of Shwachman-Diamond syndrome (SDS). The SBDS protein participates in ribosome biogenesis; however, effects beyond reduced translation efficiency are thought to be involved in SDS progression. Impaired mitochondrial function has been reported for cells lacking either SBDS or Sdo1p, the Saccharomyces cerevisiae SBDS ortholog. To better understand how the loss of SBDS/Sdo1p leads to mitochondria damage, we utilized the S. cerevisiae model of SDS. Yeast deleted for SDO1 show increased oxidative damage to mitochondrial proteins and a marked decrease in protein levels and activity of mitochondrial superoxide dismutase 2 (Sod2p), a key enzyme involved in defense against oxidants. Immature forms of Sod2p are observed in sdo1∆ cells suggesting a defect in proteolysis of the presequence. Yeast deleted for CYM1, encoding a presequence protease, display a similar reduction in Sod2p activity as sdo1∆ cells, as well as elevated oxidative damage, to mitochondrial proteins. Sod2p protein levels and activity are largely restored in a por1∆ sdo1∆ strain, lacking the major mitochondrial voltage-dependent anion channel. Together these results indicate that mitochondrial insufficiency in sdo1∆ cells may be linked to the accumulation of immature presequence containing proteins and this effect is a consequence, at least in part, from loss of counter-regulation of Por1p by Sdo1p. 2020-01-27T07:40:47Z 2020-01-27T07:40:47Z 2019-08-01 Article Journal of Cellular Biochemistry. Vol.120, No.8 (2019), 13867-13880 10.1002/jcb.28660 10974644 07302312 2-s2.0-85067311795 https://repository.li.mahidol.ac.th/handle/123456789/50111 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85067311795&origin=inward |
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Biochemistry, Genetics and Molecular Biology Laran T. Jensen The Phyu Ayushi Jain Chonlada Kaewwanna Amornrat Naranuntarat Jensen Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome |
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© 2019 Wiley Periodicals, Inc. Mutations in the human SBDS gene is the most common cause of Shwachman-Diamond syndrome (SDS). The SBDS protein participates in ribosome biogenesis; however, effects beyond reduced translation efficiency are thought to be involved in SDS progression. Impaired mitochondrial function has been reported for cells lacking either SBDS or Sdo1p, the Saccharomyces cerevisiae SBDS ortholog. To better understand how the loss of SBDS/Sdo1p leads to mitochondria damage, we utilized the S. cerevisiae model of SDS. Yeast deleted for SDO1 show increased oxidative damage to mitochondrial proteins and a marked decrease in protein levels and activity of mitochondrial superoxide dismutase 2 (Sod2p), a key enzyme involved in defense against oxidants. Immature forms of Sod2p are observed in sdo1∆ cells suggesting a defect in proteolysis of the presequence. Yeast deleted for CYM1, encoding a presequence protease, display a similar reduction in Sod2p activity as sdo1∆ cells, as well as elevated oxidative damage, to mitochondrial proteins. Sod2p protein levels and activity are largely restored in a por1∆ sdo1∆ strain, lacking the major mitochondrial voltage-dependent anion channel. Together these results indicate that mitochondrial insufficiency in sdo1∆ cells may be linked to the accumulation of immature presequence containing proteins and this effect is a consequence, at least in part, from loss of counter-regulation of Por1p by Sdo1p. |
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Mahidol University |
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Mahidol University Laran T. Jensen The Phyu Ayushi Jain Chonlada Kaewwanna Amornrat Naranuntarat Jensen |
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Article |
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Laran T. Jensen The Phyu Ayushi Jain Chonlada Kaewwanna Amornrat Naranuntarat Jensen |
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Laran T. Jensen |
title |
Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome |
title_short |
Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome |
title_full |
Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome |
title_fullStr |
Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome |
title_full_unstemmed |
Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman-Diamond syndrome |
title_sort |
decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of shwachman-diamond syndrome |
publishDate |
2020 |
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https://repository.li.mahidol.ac.th/handle/123456789/50111 |
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1763490166594338816 |