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PMID:22983063

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Citation

Stefanatos, R, Sriram, A, Kiviranta, E, Mohan, A, Ayala, V, Jacobs, HT, Pamplona, R and Sanz, A (2012) dj-1β regulates oxidative stress, insulin-like signaling and development in Drosophila melanogaster. Cell Cycle 11:3876-86

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.

Links

PubMed PMC3495829 Online version:10.4161/cc.22073

Keywords

Aging/genetics; Aging/metabolism; Animals; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/physiology; Female; Gene Expression Regulation, Developmental; Hydrogen Peroxide/metabolism; Insulin/metabolism; Longevity; Male; Mitochondria/metabolism; Mitochondrial Turnover/physiology; Motor Activity; Mutation; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Oxidation-Reduction; Oxidative Stress; Phenotype; Signal Transduction/genetics; Sirtuins/genetics; Sirtuins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:DJ1B

involved_in

GO:0010310: regulation of hydrogen peroxide metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DJ1B

involved_in

GO:0048640: negative regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VA37

involved_in

GO:0010310: regulation of hydrogen peroxide metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9VA37

involved_in

GO:0048640: negative regulation of developmental growth

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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