title: SIN3 is critical for stress resistance and modulates adult lifespan.
abstract: Coordinate control of gene activity is critical for fitness and longevity of an organism. The SIN3 histone deacetylase (HDAC) complex functions as a transcriptional repressor of many genes. SIN3-regulated genes include those that encode proteins affecting multiple aspects of mitochondrial function, such as energy production and stress responsiveness, important for health maintenance. Here we used Drosophila melanogaster as a model organism to examine the role of SIN3 in the regulation of fitness and longevity. Adult flies with RNA interference (RNAi) induced knockdown expression of Sin3A have reduced climbing ability; an activity that likely requires fully functional mitochondria. Additionally, compared to wild type, adult Sin3A knockdown flies were more sensitive to oxidative stress. Interestingly, media supplementation with the antioxidant glutathione largely restored fly tolerance to oxidative stress. Although Sin3A knockdown flies exhibited decreased longevity compared to wild type, no significant changes in expression of many well-categorized aging genes were observed. We found, however, that Sin3A knockdown corresponded to a significant reduction in expression of genes encoding proteins involved in the de novo synthesis of glutathione. Taken together, the data support a model whereby SIN3 regulates a gene expression program required for proper mitochondrial function and effective stress response during adulthood.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, 48202, USA.
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Barnes
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, 48202, USA.
authors.forename: Abhineeth
authors.initials: A
authors.lastname: Bhat
authors.affiliation: Department of Nutrition and Food Science Wayne State University, Detroit, Michigan, 48202,USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Unnikrishnan
authors.affiliation: Department of Nutrition and Food Science Wayne State University, Detroit, Michigan, 48202,USA.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Heydari
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, 48202, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Arking
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, Michigan, 48202, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Pile
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D034622:RNA Interference; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex