Stefanatos 2012 Cell Cycle: Difference between revisions
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|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: ฮฑ and ฮฒ. Dysfunction of dj-1ฮฒ strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1ฮฒ 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-1ฮฒ 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-1ฮฒ mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1ฮฒ in oxidative stress handling, 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: ฮฑ and ฮฒ. Dysfunction of dj-1ฮฒ strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1ฮฒ 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-1ฮฒ 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-1ฮฒ mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1ฮฒ in oxidative stress handling, insulin-like signaling and development in Drosophila melanogaster. | ||
|keywords=Mitochondria, dj-1 ฮฒ , Oxidative stress, Drosophila, Lifespan | |keywords=Mitochondria, dj-1 ฮฒ , Oxidative stress, Drosophila, Lifespan | ||
|mipnetlab=UK Newcastle Sanz A, FI Tampere Dufour E | |mipnetlab=UK Newcastle Sanz A, FI Tampere Dufour E, FI Helsinki Jacobs HT | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
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|preparations=Isolated mitochondria | |preparations=Isolated mitochondria | ||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
| | |pathways=N, CIV | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 15:27, 26 March 2018
Stefanatos R, Sriram A, Kiviranta E, Mohan A, Ayala V, Jacobs HT, Pamplona R, Sanz A (2012) dj-1ฮฒ regulates oxidative stress, insulin-like signaling and development in Drosophila melanogaster. Cell Cycle 11:3876-86. |
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: ฮฑ and ฮฒ. Dysfunction of dj-1ฮฒ strongly impairs fly mobility in an age-dependent manner. In this study, we analyze in detail the molecular mechanism underlying the dj-1ฮฒ 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-1ฮฒ 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-1ฮฒ mutation unexpectedly accelerated development, a phenotype not previously associated with this mutation. Our results reveal an important role of dj-1ฮฒ in oxidative stress handling, insulin-like signaling and development in Drosophila melanogaster. โข Keywords: Mitochondria, dj-1 ฮฒ, Oxidative stress, Drosophila, Lifespan
โข O2k-Network Lab: UK Newcastle Sanz A, FI Tampere Dufour E, FI Helsinki Jacobs HT
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Drosophila
Preparation: Isolated mitochondria
Coupling state: OXPHOS
Pathway: N, CIV
HRR: Oxygraph-2k