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...
Published in: | PLoS ONE |
---|---|
Main Authors: | , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Sciene
2013
|
Subjects: | |
Online Access: | https://lirias.kuleuven.be/handle/123456789/434915 https://doi.org/10.1371/journal.pone.0072844 |
id |
ftunivleuven:oai:lirias.kuleuven.be:123456789/434915 |
---|---|
record_format |
openpolar |
spelling |
ftunivleuven:oai:lirias.kuleuven.be:123456789/434915 2023-05-15T16:05:20+02:00 Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution Van der Eecken, Valérie Clippe, André Dekoninck, Sophie Goemaere, Julie Walbrecq, Geoffroy Van Veldhoven, Paul P Knoops, Bernard 2013 https://lirias.kuleuven.be/handle/123456789/434915 https://doi.org/10.1371/journal.pone.0072844 en eng Public Library of Sciene PLoS One vol:8 issue:9 pages:e72844 https://lirias.kuleuven.be/handle/123456789/434915 1932-6203 http://dx.plos.org/10.1371/journal.pone.0072844 Description (Metadata) only IT article 2013 ftunivleuven https://doi.org/10.1371/journal.pone.0072844 2015-12-22T16:38:43Z 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. status: published Article in Journal/Newspaper Elephant Seal KU Leuven: Lirias Darby ENVELOPE(162.217,162.217,-77.667,-77.667) PLoS ONE 8 9 e72844 |
institution |
Open Polar |
collection |
KU Leuven: Lirias |
op_collection_id |
ftunivleuven |
language |
English |
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. status: published |
format |
Article in Journal/Newspaper |
author |
Van der Eecken, Valérie Clippe, André Dekoninck, Sophie Goemaere, Julie Walbrecq, Geoffroy Van Veldhoven, Paul P Knoops, Bernard |
spellingShingle |
Van der Eecken, Valérie Clippe, André Dekoninck, Sophie Goemaere, Julie Walbrecq, Geoffroy Van Veldhoven, Paul P Knoops, Bernard Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution |
author_facet |
Van der Eecken, Valérie Clippe, André Dekoninck, Sophie Goemaere, Julie Walbrecq, Geoffroy Van Veldhoven, Paul P Knoops, Bernard |
author_sort |
Van der Eecken, Valérie |
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 Sciene |
publishDate |
2013 |
url |
https://lirias.kuleuven.be/handle/123456789/434915 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_relation |
PLoS One vol:8 issue:9 pages:e72844 https://lirias.kuleuven.be/handle/123456789/434915 1932-6203 http://dx.plos.org/10.1371/journal.pone.0072844 |
op_doi |
https://doi.org/10.1371/journal.pone.0072844 |
container_title |
PLoS ONE |
container_volume |
8 |
container_issue |
9 |
container_start_page |
e72844 |
_version_ |
1766401237917368320 |