Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution.
peer reviewed In human, the subcellular targeting of peroxiredoxin-5 (PRDX5), a thioredoxin peroxidase, is dependent on the use of multiple alternative transcription start sites and two alternative in-frame translation initiation sites, which determine whether or not the region encoding a mitochondr...
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Online Access: | https://orbilu.uni.lu/handle/10993/26378 https://doi.org/10.1371/journal.pone.0072844 |
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ftunivluxembourg:oai:orbilu.uni.lu:10993/26378 2024-10-13T14:06:56+00:00 Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. Van der Eecken, Valerie Clippe, Andre Dekoninck, Sophie Goemaere, Julie WALBRECQ, Geoffroy Van Veldhoven, Paul P. Knoops, Bernard 2013 https://orbilu.uni.lu/handle/10993/26378 https://doi.org/10.1371/journal.pone.0072844 en eng Public Library of Science urn:issn:1932-6203 https://orbilu.uni.lu/handle/10993/26378 info:hdl:10993/26378 doi:10.1371/journal.pone.0072844 info:pmid:24023783 wos:000324238400027 restricted access http://purl.org/coar/access_right/c_16ec info:eu-repo/semantics/restrictedAccess PLoS ONE, 8 (9), e72844 (2013) Amino Acid Sequence Animals Cell Line Dogs Humans Molecular Sequence Data Oxidative Stress/genetics/physiology Peroxiredoxins/chemistry/genetics/metabolism Life sciences Biochemistry biophysics & molecular biology Sciences du vivant Biochimie biophysique & biologie moléculaire journal article http://purl.org/coar/resource_type/c_6501 info:eu-repo/semantics/article peer reviewed 2013 ftunivluxembourg https://doi.org/10.1371/journal.pone.0072844 2024-09-27T07:04:14Z peer reviewed In human, the subcellular targeting of peroxiredoxin-5 (PRDX5), a thioredoxin peroxidase, is dependent on the use of multiple alternative transcription start sites and two alternative in-frame translation initiation sites, which determine whether or not the region encoding a mitochondrial targeting sequence (MTS) is translated. In the present study, the abolition of PRDX5 mitochondrial targeting in dog is highlighted and the molecular mechanism underlying the loss of mitochondrial PRDX5 during evolution is examined. Here, we show that the absence of mitochondrial PRDX5 is generalized among the extant canids and that the first events leading to PRDX5 MTS abolition in canids involve a mutation in the more 5' translation initiation codon as well as the appearance of a STOP codon. Furthermore, we found that PRDX5 MTS functionality is maintained in giant panda and northern elephant seal, which are phylogenetically closely related to canids. Also, the functional consequences of the restoration of mitochondrial PRDX5 in dog Madin-Darby canine kidney (MDCK) cells were investigated. The restoration of PRDX5 mitochondrial targeting in MDCK cells, instead of protecting, provokes deleterious effects following peroxide exposure independently of its peroxidase activity, indicating that mitochondrial PRDX5 gains cytotoxic properties under acute oxidative stress in MDCK cells. Altogether our results show that, although mitochondrial PRDX5 cytoprotective function against oxidative stress has been clearly demonstrated in human and rodents, PRDX5 targeting to mitochondria has been evolutionary lost in canids. Moreover, restoration of mitochondrial PRDX5 in dog MDCK cells, instead of conferring protection against peroxide exposure, makes them more vulnerable. Article in Journal/Newspaper Elephant Seal University of Luxembourg: ORBilu - Open Repository and Bibliography Darby ENVELOPE(162.217,162.217,-77.667,-77.667) PLoS ONE 8 9 e72844 |
institution |
Open Polar |
collection |
University of Luxembourg: ORBilu - Open Repository and Bibliography |
op_collection_id |
ftunivluxembourg |
language |
English |
topic |
Amino Acid Sequence Animals Cell Line Dogs Humans Molecular Sequence Data Oxidative Stress/genetics/physiology Peroxiredoxins/chemistry/genetics/metabolism Life sciences Biochemistry biophysics & molecular biology Sciences du vivant Biochimie biophysique & biologie moléculaire |
spellingShingle |
Amino Acid Sequence Animals Cell Line Dogs Humans Molecular Sequence Data Oxidative Stress/genetics/physiology Peroxiredoxins/chemistry/genetics/metabolism Life sciences Biochemistry biophysics & molecular biology Sciences du vivant Biochimie biophysique & biologie moléculaire Van der Eecken, Valerie Clippe, Andre Dekoninck, Sophie Goemaere, Julie WALBRECQ, Geoffroy Van Veldhoven, Paul P. Knoops, Bernard Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
topic_facet |
Amino Acid Sequence Animals Cell Line Dogs Humans Molecular Sequence Data Oxidative Stress/genetics/physiology Peroxiredoxins/chemistry/genetics/metabolism Life sciences Biochemistry biophysics & molecular biology Sciences du vivant Biochimie biophysique & biologie moléculaire |
description |
peer reviewed In human, the subcellular targeting of peroxiredoxin-5 (PRDX5), a thioredoxin peroxidase, is dependent on the use of multiple alternative transcription start sites and two alternative in-frame translation initiation sites, which determine whether or not the region encoding a mitochondrial targeting sequence (MTS) is translated. In the present study, the abolition of PRDX5 mitochondrial targeting in dog is highlighted and the molecular mechanism underlying the loss of mitochondrial PRDX5 during evolution is examined. Here, we show that the absence of mitochondrial PRDX5 is generalized among the extant canids and that the first events leading to PRDX5 MTS abolition in canids involve a mutation in the more 5' translation initiation codon as well as the appearance of a STOP codon. Furthermore, we found that PRDX5 MTS functionality is maintained in giant panda and northern elephant seal, which are phylogenetically closely related to canids. Also, the functional consequences of the restoration of mitochondrial PRDX5 in dog Madin-Darby canine kidney (MDCK) cells were investigated. The restoration of PRDX5 mitochondrial targeting in MDCK cells, instead of protecting, provokes deleterious effects following peroxide exposure independently of its peroxidase activity, indicating that mitochondrial PRDX5 gains cytotoxic properties under acute oxidative stress in MDCK cells. Altogether our results show that, although mitochondrial PRDX5 cytoprotective function against oxidative stress has been clearly demonstrated in human and rodents, PRDX5 targeting to mitochondria has been evolutionary lost in canids. Moreover, restoration of mitochondrial PRDX5 in dog MDCK cells, instead of conferring protection against peroxide exposure, makes them more vulnerable. |
format |
Article in Journal/Newspaper |
author |
Van der Eecken, Valerie Clippe, Andre Dekoninck, Sophie Goemaere, Julie WALBRECQ, Geoffroy Van Veldhoven, Paul P. Knoops, Bernard |
author_facet |
Van der Eecken, Valerie Clippe, Andre Dekoninck, Sophie Goemaere, Julie WALBRECQ, Geoffroy Van Veldhoven, Paul P. Knoops, Bernard |
author_sort |
Van der Eecken, Valerie |
title |
Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
title_short |
Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
title_full |
Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
title_fullStr |
Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
title_full_unstemmed |
Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
title_sort |
abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
publisher |
Public Library of Science |
publishDate |
2013 |
url |
https://orbilu.uni.lu/handle/10993/26378 https://doi.org/10.1371/journal.pone.0072844 |
long_lat |
ENVELOPE(162.217,162.217,-77.667,-77.667) |
geographic |
Darby |
geographic_facet |
Darby |
genre |
Elephant Seal |
genre_facet |
Elephant Seal |
op_source |
PLoS ONE, 8 (9), e72844 (2013) |
op_relation |
urn:issn:1932-6203 https://orbilu.uni.lu/handle/10993/26378 info:hdl:10993/26378 doi:10.1371/journal.pone.0072844 info:pmid:24023783 wos:000324238400027 |
op_rights |
restricted access http://purl.org/coar/access_right/c_16ec info:eu-repo/semantics/restrictedAccess |
op_doi |
https://doi.org/10.1371/journal.pone.0072844 |
container_title |
PLoS ONE |
container_volume |
8 |
container_issue |
9 |
container_start_page |
e72844 |
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1812813175468326912 |