Article (Scientific journals)
Phosphorylation of HtrA2 by cyclin-dependent kinase-5 is important for mitochondrial function.
Fitzgerald, J. C.; Camprubi, M. D.; Dunn, L. et al.
2012In Cell Death and Differentiation, 19 (2), p. 257-66
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Keywords :
Animals; Cyclin-Dependent Kinase 5/metabolism; Cytosol/metabolism; Humans; Mice; Mitochondria/enzymology; Mitochondrial Proteins/chemistry/metabolism; Phosphorylation; Phosphoserine/metabolism; Protein Binding; Protein Transport; Serine Endopeptidases/chemistry/metabolism
Abstract :
[en] 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 (S142 and S400) have been found in Parkinson's disease patients. However, the mechanism of this neuroprotection and the signalling pathways associated with it remain mostly unknown. Here we report that cyclin-dependent kinase-5 (Cdk5), a kinase implicated in the pathogenesis of several neurodegenerative diseases, is responsible for phosphorylating HtrA2 at S400. HtrA2 and Cdk5 interact in human and mouse cell lines and brain, and Cdk5 phosphorylates S400 on HtrA2 in a p38-dependent 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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Fitzgerald, J. C.
Camprubi, M. D.
Dunn, L.
Wu, H.-C.
Ip, N. Y.
Krüger, Rejko ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Martins, Luisa 
Wood, N. W.
Plun-Favreau, H.
Language :
Title :
Phosphorylation of HtrA2 by cyclin-dependent kinase-5 is important for mitochondrial function.
Publication date :
Journal title :
Cell Death and Differentiation
Publisher :
Nature Publishing Group, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
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