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

TitleDrosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin.
Publication TypeJournal Article
Year of Publication2009
AuthorsTain, LS, Chowdhury, RB, Tao, RN, Plun-Favreau, H, Moisoi, N, Martins, LM, Downward, J, Whitworth, AJ, Tapon, N
JournalCell Death Differ
Volume16
Issue8
Pagination1118-25
Date Published2009 Aug
ISSN1476-5403
KeywordsAnimals, Animals, Genetically Modified, Animals, Newborn, Apoptosis, Drosophila, Drosophila Proteins, Female, Fertility, Male, Mitochondria, Mutant Proteins, Mutation, Phosphorylation, Protein-Serine-Threonine Kinases, Serine Endopeptidases, Ubiquitin-Protein Ligases
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.

DOI10.1038/cdd.2009.23
Alternate JournalCell Death Differ.
Citation Key10.1038/cdd.2009.23
PubMed ID19282869
PubMed Central IDPMC2711053
Grant List081987 / / Wellcome Trust / United Kingdom
081987 / / Wellcome Trust / United Kingdom
A5305 / / Cancer Research UK / United Kingdom
G-0713 / / Parkinson's UK / United Kingdom
G-4063 / / Parkinson's UK / United Kingdom
G0700183 / / Medical Research Council / United Kingdom
G070091 / / Medical Research Council / United Kingdom
GR077544AIA / / Wellcome Trust / United Kingdom
MC_U132674518 / / Medical Research Council / United Kingdom
/ / Cancer Research UK / United Kingdom