Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin
Open Access
- 13 March 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 16 (8), 1118-1125
- https://doi.org/10.1038/cdd.2009.23
Abstract
High Temperature Requirement A2 (HtrA2/Omi) is a mitochondrial protease that exhibits pro-apoptotic and cell protective properties and has been linked to Parkinson 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.This publication has 58 references indexed in Scilit:
- Implementing a systems-oriented morbidity and mortality conference in remote rural Nepal for quality improvementBMJ Quality & Safety, 2011
- The hospital standardised mortality ratio: a powerful tool for Dutch hospitals to assess their quality of care?Quality and Safety in Health Care, 2010
- Loss-of-Function Analysis Suggests ThatOmi/HtrA2Is Not an Essential Component of thepink1/parkinPathwayIn VivoJournal of Neuroscience, 2008
- Genetic variation of Omi/HtrA2 and Parkinson's diseaseParkinsonism & Related Disorders, 2008
- Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson’s disease factors Pink1 and ParkinDisease Models & Mechanisms, 2008
- Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controlsHuman Molecular Genetics, 2008
- The interaction of DIAP1 with dOmi/HtrA2 regulates cell death in DrosophilaCell Death & Differentiation, 2008
- Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine proteaseThe EMBO Journal, 2007
- What is "quality improvement" and how can it transform healthcare?Quality and Safety in Health Care, 2007
- Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by ParkinProceedings of the National Academy of Sciences of the United States of America, 2006