title: Glutathione S-transferase omega suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila.
abstract: Loss-of-function mutation of the PTEN-induced kinase 1 (PINK1) gene is a common cause of early-onset Parkinson's disease (PD). Glutathione S-transferase omega (GSTO) is a phase II detoxification enzyme that conjugates targets to glutathione, and has recently been implicated in parkin-associated PD. In this study, we found Drosophila GstO2 to be a novel genetic suppressor of the PINK1 loss-of-function mutant. We show that GstO2A expression is reduced in PINK1 mutants. Moreover, the upregulation of GstO2A restores muscle degeneration and dopaminergic neuron loss in PINK1 mutants. Given the previous data of a reduced expression of GstO2A and decreased glutathionylation of ATP synthase β subunit in parkin or PINK1 mutants, these results suggest that the function of GstO2 is regulated by the PINK1/parkin pathway and that GstO2 also has a protective role in PINK1-associated PD.
authors.affiliation: Department of Medical Biotechnology, Soonchunhyang University, Asan-si, Republic of Korea. kiyoung2@sch.ac.kr
authors.forename: Kiyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Jeongbin
authors.initials: J
authors.lastname: Yim
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D059290:Dopaminergic Neurons / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D005982:Glutathione Transferase / Q000378:metabolism*; D006706:Homeostasis; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D029721:Drosophila Proteins; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase; C487430:park protein, Drosophila
keywords: Dopaminergic neuron; Drosophila; Glutathione S-transferase omega; PINK1; Parkinson disease