Reference Report

Reference
Citation	Tain, L.S., Chowdhury, R.B., Tao, R.N., Plun-Favreau, H., Moisoi, N., Martins, L.M., Downward, J., Whitworth, A.J., Tapon, N. (2009). Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin. Cell Death Differ. 16(8): 1118--1125. (Export to RIS)
FlyBase ID	FBrf0208357
Publication Type	Research paper
PubMed ID	19282869
PubMed 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.
DOI	10.1038/cdd.2009.23
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Secondary IDs
Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Cell Death Differ.
Title	Cell Death and Differentiation
Publication Year	1994-
ISBN/ISSN	1350-9047
Data from Reference
Aberrations (1)
	Df(3R)HtrA2^Δ1
Alleles (10)
	HtrA2^+t2.5 HtrA2^{Scer\UAS.P\T.cTa} HtrA2^Δ1 mRpL11^+t2.0 mRpL11^G4907 mRpL11^Δ1 park²⁵ Pink1^B9 Scer\GAL4^Act.PU w^+mC
Constructs (5)
	P{Act-GAL4.U} P{EP} P{HtrA2^+t2.5} P{mRpL11^+t2.0} P{UASp-HtrA2.T}
Genes (6)
	HtrA2 mRpL11 park Pink1 Scer\GAL4 w
Insertions (1)
	P{EP}mRpL11^G4907
Natural transposons (1)
	P-element