title: The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan inSaccharomyces cerevisiae.
abstract: Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan inC. elegansandS. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Sir2p, the founding member of the Sirtuin family of lifespan regulators, also affects actin cable dynamics, assembly, and function in mitochondrial quality control. Here, we obtained evidence for novel interactions between Sir2p and Sum1p, a transcriptional repressor that was originally identified through mutations that genetically suppresssir2∆ phenotypes unrelated to lifespan. We find that deletion ofSUM1in wild-type cells results in increased mitochondrial function and actin cable abundance. Furthermore, deletion ofSUM1suppresses defects in actin cables and mitochondria ofsir2∆ yeast, and extends the replicative lifespan and cellular health span ofsir2∆ cells. Thus, Sum1p suppresses Sir2p function in control of specific aging determinants and lifespan in budding yeast.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
authors.forename: Ryo
authors.initials: R
authors.lastname: Higuchi-Sanabria
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. ; Current address: Department of Neuroscience, University of Wisconsin, Madison, WI, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Vevea
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. ; Current address: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Charalel
authors.affiliation: Department of Biological Sciences, Hunter College and The Graduate Center Biochemistry, Biology and Biopsychology and Behavioral Neuroscience Programs, CUNY, New York, NY 10065, USA. Current address: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Sapar
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. ; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Liza A
authors.initials: LA
authors.lastname: Pon
keywords: actin cytoskeleton; aging; mitochondria; sirtuin