Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution.
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...
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ftdoajarticles:oai:doaj.org/article:9f52ae0204ed4aeda6bfb531b3e1eccb 2023-05-15T16:05:22+02:00 Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. Valérie Van der Eecken André Clippe Sophie Dekoninck Julie Goemaere Geoffroy Walbrecq Paul P Van Veldhoven Bernard Knoops 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0072844 https://doaj.org/article/9f52ae0204ed4aeda6bfb531b3e1eccb EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3759418?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0072844 https://doaj.org/article/9f52ae0204ed4aeda6bfb531b3e1eccb PLoS ONE, Vol 8, Iss 9, p e72844 (2013) Medicine R Science Q article 2013 ftdoajarticles https://doi.org/10.1371/journal.pone.0072844 2022-12-31T04:46:52Z 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 Directory of Open Access Journals: DOAJ Articles Darby ENVELOPE(162.217,162.217,-77.667,-77.667) PLoS ONE 8 9 e72844 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Medicine R Science Q |
spellingShingle |
Medicine R Science Q Valérie Van der Eecken André Clippe Sophie Dekoninck Julie Goemaere Geoffroy Walbrecq Paul P Van Veldhoven Bernard Knoops Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution. |
topic_facet |
Medicine R Science Q |
description |
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 |
Valérie Van der Eecken André Clippe Sophie Dekoninck Julie Goemaere Geoffroy Walbrecq Paul P Van Veldhoven Bernard Knoops |
author_facet |
Valérie Van der Eecken André Clippe Sophie Dekoninck Julie Goemaere Geoffroy Walbrecq Paul P Van Veldhoven Bernard Knoops |
author_sort |
Valérie Van der Eecken |
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 (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pone.0072844 https://doaj.org/article/9f52ae0204ed4aeda6bfb531b3e1eccb |
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, Vol 8, Iss 9, p e72844 (2013) |
op_relation |
http://europepmc.org/articles/PMC3759418?pdf=render https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0072844 https://doaj.org/article/9f52ae0204ed4aeda6bfb531b3e1eccb |
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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1766401258137059328 |