Stefanatos 2012 Cell Cycle
| Stefanatos R, Sriram A, Kiviranta E, Mohan A, Ayala V, Jacobs HT, Pamplona R, Sanz A (2012) dj-1Ξ² regulates oxidative stress, insulin-like signaling and development in Drosophila melanogaster. Cell Cycle 11: 3876-3886. |
Stefanatos R, Sriram A, Kiviranta E, Mohan A, Ayala V, Jacobs HT, Pamplona R, Sanz A (2012) Cell Cycle
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: Ξ± and Ξ². Dysfunction of dj-1Ξ² strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1Ξ² 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-1Ξ² 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-1Ξ² mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1Ξ² in oxidative stress handling, insulin-like signaling and development in Drosophila melanogaster. β’ Keywords: Mitochondria, dj-1 Ξ², Oxidative stress, Drosophila, Lifespan
β’ O2k-Network Lab: UK Newcastle Sanz A, FI Tampere Dufour E
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Drosophila
Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
Coupling state: OXPHOS
HRR: Oxygraph-2k
