Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin

Tain, L. S., Chowdhury, Ruhena B., Tao, R. N., Plun-Favreau, H., Moisoi, N., Martins, L. M., Downward, J., Whitworth, A. J. and Tapon, N. 2009. Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin. Cell Death and Differentiation 16 (8) , pp. 1118-1125. 10.1038/cdd.2009.23

Full text not available from this repository.

Abstract

High temperature requirement A2 (HtrA2/Omi) is a mitochondrial protease that exhibits proapoptotic and cell-protective properties and has been linked to Parkinson's disease (PD). Impaired mitochondrial function is a common trait in PD patients, and is likely to play a significant role in pathogenesis of parkinsonism, but the molecular mechanisms remain poorly understood. Genetic studies in Drosophila have provided valuable insight into the function of other PD-linked genes, in particular PINK1 and parkin, and their role in maintaining mitochondrial integrity. Recently, HtrA2 was shown to be phosphorylated in a PINK1-dependent manner, suggesting it might act in the PINK1 pathway. Here, we describe the characterization of mutations in Drosophila HtrA2, and genetic analysis of its function with PINK1 and parkin. Interestingly, we find HtrA2 appears to be dispensable for developmental or stress-induced apoptosis. In addition, we found HtrA2 mutants share some phenotypic similarities with parkin and PINK1 mutants, suggesting that it may function in maintaining mitochondrial integrity. Our genetic interaction studies, including analysis of double-mutant combinations and epistasis experiments, suggest HtrA2 acts downstream of PINK1 but in a pathway parallel to Parkin.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	HtrA2, Omi, PINK1, Parkinson's disease, Drosophila, apoptosis, mitochondria
Publisher:	Nature Publishing Group
ISSN:	1350-9047
Last Modified:	19 Mar 2016 22:53
URI:	https://orca.cardiff.ac.uk/id/eprint/30183

Citation Data

Cited 73 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item