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. 2007 Nov;9(11):1243-52.
doi: 10.1038/ncb1644. Epub 2007 Sep 30.

The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1

Hélène Plun-Favreau  1 , Kristina Klupsch, Nicoleta Moisoi, Sonia Gandhi, Svend Kjaer, David Frith, Kirsten Harvey, Emma Deas, Robert J Harvey, Neil McDonald, Nicholas W Wood, L Miguel Martins, Julian Downward
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The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1

Hélène Plun-Favreau et al. Nat Cell Biol. 2007 Nov.

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.

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