The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
Identifieur interne : 000F36 ( Main/Exploration ); précédent : 000F35; suivant : 000F37The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1
Auteurs : Hlne Plun-Favreau [Royaume-Uni] ; Kristina Klupsch [Royaume-Uni] ; Nicoleta Moisoi [Royaume-Uni] ; Sonia Gandhi [Royaume-Uni] ; Svend Kjaer [Royaume-Uni] ; David Frith [Royaume-Uni] ; Kirsten Harvey [Royaume-Uni] ; Emma Deas [Royaume-Uni] ; Robert J. Harvey [Royaume-Uni] ; Neil Mcdonald [Royaume-Uni] ; Nicholas W. Wood [Royaume-Uni] ; L. Miguel Martins [Royaume-Uni] ; Julian Downward [Royaume-Uni]Source :
- Nature Cell Biology [ 1465-7392 ] ; 2007-11.
Abstract
In mice, targeted deletion of the serine protease HtrA2 (also known as Omi) causes mitochondrial dysfunction leading to a neurodegenerative disorder with parkinsonian features. In humans, point mutations in HtrA2 are a susceptibility factor for Parkinson's disease (PARK13 locus). Mutations in PINK1, a putative mitochondrial protein kinase, are associated with the PARK6 autosomal recessive locus for susceptibility to early-onset Parkinson's disease. Here we determine that HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway. HtrA2 is phosphorylated on activation of the p38 pathway, occurring in a PINK1-dependent manner at a residue adjacent to a position found mutated in patients with Parkinson's disease. HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1. We suggest that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.
Url:
DOI: 10.1038/ncb1644
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In humans, point mutations in HtrA2 are a susceptibility factor for Parkinson's disease (PARK13 locus). Mutations in PINK1, a putative mitochondrial protein kinase, are associated with the PARK6 autosomal recessive locus for susceptibility to early-onset Parkinson's disease. Here we determine that HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway. HtrA2 is phosphorylated on activation of the p38 pathway, occurring in a PINK1-dependent manner at a residue adjacent to a position found mutated in patients with Parkinson's disease. HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1. We suggest that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Plun Favreau, Hlne" sort="Plun Favreau, Hlne" uniqKey="Plun Favreau H" first="Hlne" last="Plun-Favreau">Hlne Plun-Favreau</name></noRegion><name sortKey="Deas, Emma" sort="Deas, Emma" uniqKey="Deas E" first="Emma" last="Deas">Emma Deas</name><name sortKey="Downward, Julian" sort="Downward, Julian" uniqKey="Downward J" first="Julian" last="Downward">Julian Downward</name><name sortKey="Downward, Julian" sort="Downward, Julian" uniqKey="Downward J" first="Julian" last="Downward">Julian Downward</name><name sortKey="Frith, David" sort="Frith, David" uniqKey="Frith D" first="David" last="Frith">David Frith</name><name sortKey="Gandhi, Sonia" sort="Gandhi, Sonia" uniqKey="Gandhi S" first="Sonia" last="Gandhi">Sonia Gandhi</name><name sortKey="Harvey, Kirsten" sort="Harvey, Kirsten" uniqKey="Harvey K" first="Kirsten" last="Harvey">Kirsten Harvey</name><name sortKey="Harvey, Robert J" sort="Harvey, Robert J" uniqKey="Harvey R" first="Robert J." last="Harvey">Robert J. Harvey</name><name sortKey="Kjaer, Svend" sort="Kjaer, Svend" uniqKey="Kjaer S" first="Svend" last="Kjaer">Svend Kjaer</name><name sortKey="Klupsch, Kristina" sort="Klupsch, Kristina" uniqKey="Klupsch K" first="Kristina" last="Klupsch">Kristina Klupsch</name><name sortKey="Martins, L Miguel" sort="Martins, L Miguel" uniqKey="Martins L" first="L. Miguel" last="Martins">L. Miguel Martins</name><name sortKey="Martins, L Miguel" sort="Martins, L Miguel" uniqKey="Martins L" first="L. Miguel" last="Martins">L. Miguel Martins</name><name sortKey="Mcdonald, Neil" sort="Mcdonald, Neil" uniqKey="Mcdonald N" first="Neil" last="Mcdonald">Neil Mcdonald</name><name sortKey="Moisoi, Nicoleta" sort="Moisoi, Nicoleta" uniqKey="Moisoi N" first="Nicoleta" last="Moisoi">Nicoleta Moisoi</name><name sortKey="Plun Favreau, Hlne" sort="Plun Favreau, Hlne" uniqKey="Plun Favreau H" first="Hlne" last="Plun-Favreau">Hlne Plun-Favreau</name><name sortKey="Wood, Nicholas W" sort="Wood, Nicholas W" uniqKey="Wood N" first="Nicholas W." last="Wood">Nicholas W. Wood</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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