Phosphorylation of HtrA2 by Cyclin Dependant Kinase 5 is important for mitochondrial function.

Helene Plun-Favreau (1) , Julia Fitzgerald (1) , Marta Delgado Campubri (1) , Laura Dunn (1) , Hsiu-Chuan Wu (1) , Nancy Ip (1) , Rejko Krüger (1) , L. Miguel Martins (1) , Nicholas Wood (1)

1 Department of Molecular Neuroscience

The role of the serine protease HtrA2 in neuroprotection was initially identified by the demonstration of neurodegeneration in mice lacking HtrA2 expression or function and the interesting finding that mutations adjacent to two putative phosphorylation sites (serines 142 and 400) have been found in Parkinson's disease (PD) patients. However, the mechanism of this neuroprotection and the signalling pathways associated with it remain mostly unknown. Here we report that cyclin dependant kinase 5 (Cdk5), a kinase implicated in the pathogenesis of several neurodegenerative diseases, is responsible for phosphorylating HtrA2 at serine 400 [S400]. HtrA2 and Cdk5 interact in human and mouse cell lines and brain and Cdk5 phosphorylates S400 on HtrA2 in a p38 dependant manner. Phosphorylation of HtrA2 at S400 is involved in maintaining mitochondrial membrane potential under stress conditions and is important for mitochondrial function, conferring cells protection against cellular stress.

Mots clés: HtrA2; Cdk5; Phosphorylation; Mitochondria

Helene Plun-Favreau, Julia Fitzgerald, Marta Delgado Campubri, Laura Dunn, Hsiu-Chuan Wu, et al.. Phosphorylation of HtrA2 by Cyclin Dependant Kinase 5 is important for mitochondrial function.. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2011.90⟩. ⟨hal-00654944⟩