Stefanatos 2012 Cell Cycle

From Bioblast
Publications in the MiPMap
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 11:3876-86.

Β» PMID: 22983063

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, FI Helsinki Jacobs HT


Labels: MiParea: Respiration, Genetic knockout;overexpression 


Organism: Drosophila 

Preparation: Isolated mitochondria 


Coupling state: OXPHOS  Pathway: N, CIV  HRR: Oxygraph-2k 


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