title: The Swi3 protein plays a unique role in regulating respiration in eukaryotes.
abstract: Recent experimental evidence increasingly shows that the dysregulation of cellular bioenergetics is associated with a wide array of common human diseases, including cancer, neurological diseases and diabetes. Respiration provides a vital source of cellular energy for most eukaryotic cells, particularly high energy demanding cells. However, the understanding of how respiration is globally regulated is very limited. Interestingly, recent evidence suggests that Swi3 is an important regulator of respiration genes in yeast. In this report, we performed an array of biochemical and genetic experiments and computational analysis to directly evaluate the function of Swi3 and its human homologues in regulating respiration. First, we showed, by computational analysis and measurements of oxygen consumption and promoter activities, that Swi3, not Swi2, regulates genes encoding functions involved in respiration and oxygen consumption. Biochemical analysis showed that the levels of mitochondrial respiratory chain complexes were substantially increased in Δswi3 cells, compared with the parent cells. Additionally, our data showed that Swi3 strongly affects haem/oxygen-dependent activation of respiration gene promoters whereas Swi2 affects only the basal, haem-independent activities of these promoters. We found that increased expression of aerobic expression genes is correlated with increased oxygen consumption and growth rates in Δswi3 cells in air. Furthermore, using computational analysis and RNAi knockdown, we showed that the mammalian Swi3 BAF155 and BAF170 regulate respiration in HeLa cells. Together, these experimental and computational data demonstrated that Swi3 and its mammalian homologues are key regulators in regulating respiration.
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A.
authors.forename: Sneha
authors.initials: S
authors.lastname: Lal
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A.
authors.forename: Md Maksudul
authors.initials: MM
authors.lastname: Alam
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A.
authors.forename: Jagmohan
authors.initials: J
authors.lastname: Hooda
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A.
authors.forename: Ajit
authors.initials: A
authors.lastname: Shah
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A.
authors.forename: Thai M
authors.initials: TM
authors.lastname: Cao
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xuan
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Mail Stop RL11, 800 W. Campbell Road, Richardson, TX 75080, U.S.A. li.zhang@utdallas.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D010101:Oxygen Consumption / Q000235:genetics; D011401:Promoter Regions, Genetic; D012119:Respiration / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C101681:SMARCC1 protein, human; C101682:SMARCC2 protein, human; C072981:SWI3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases; C499333:SNF2 protein, S cerevisiae
keywords: BAF155; BAF170; Swi3; aerobic respiration; bioenergetics; oxygen consumption