title: dj-1β regulates oxidative stress, insulin-like signaling and development in Drosophila melanogaster.
abstract: DJ-1 (or PARK-7) is a multifunctional protein implicated in numerous pathologies including cancer, sterility and Parkinson disease (PD). The popular genetic model Drosophila melanogaster has two orthologs, dj-1: α and β. Dysfunction of dj-1β strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1β mutant phenotype. Mitochondrial hydrogen peroxide production, but not superoxide production, was increased in mutant flies. An increase in peroxide leak from mitochondria causes oxidative damage elsewhere and explains the strong reduction in mobility caused by dj-1β mutation. However, at the same time, increased levels of hydrogen peroxide activated a pro-survival program characterized by (1) an alteration in insulin-like signaling, (2) an increase in mitochondrial biogenesis and (3) an increase in the de-acetylase activity of sirtuins. The activation of this pro-survival program was associated with increased longevity under conditions of moderate oxidative stress. Additionally, the dj-1β mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1β in oxidative stress handling, insulin-like signaling and development in Drosophila melanogaster.
authors.affiliation: Institute of Biomedical Technology and Tampere University Hospital, University of Tampere, Tampere, Finland.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Stefanatos
authors.forename: Ashwin
authors.initials: A
authors.lastname: Sriram
authors.forename: Essi
authors.initials: E
authors.lastname: Kiviranta
authors.forename: Aravind
authors.initials: A
authors.lastname: Mohan
authors.forename: Victoria
authors.initials: V
authors.lastname: Ayala
authors.forename: Howard T
authors.initials: HT
authors.lastname: Jacobs
authors.forename: Reinald
authors.initials: R
authors.lastname: Pamplona
authors.forename: Alberto
authors.initials: A
authors.lastname: Sanz
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008136:Longevity; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000502:physiology; D009043:Motor Activity; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010641:Phenotype; D000071617:Protein Deglycase DJ-1; D015398:Signal Transduction / Q000235:genetics; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D006861:Hydrogen Peroxide; C506879:DJ-1beta protein, Drosophila; D000071617:Protein Deglycase DJ-1; D037761:Sirtuins