title: Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.
abstract: Although environmental stress likely plays a significant role in promoting aging, the relationship remains poorly understood. To characterize this interaction in a more comprehensive manner, we examined the stress response profiles for 46 long-lived yeast mutant strains across four different stress conditions (oxidative, ER, DNA damage, and thermal), grouping genes based on their associated stress response profiles. Unexpectedly, cells lacking the mitochondrial AAA protease gene AFG3 clustered strongly with long-lived strains lacking cytosolic ribosomal proteins of the large subunit. Similar to these ribosomal protein mutants, afg3Δ cells show reduced cytoplasmic mRNA translation, enhanced resistance to tunicamycin that is independent of the ER unfolded protein response, and Sir2-independent but Gcn4-dependent lifespan extension. These data demonstrate an unexpected link between a mitochondrial protease, cytoplasmic mRNA translation, and aging.
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Joe R
authors.initials: JR
authors.lastname: Delaney
authors.forename: Umema
authors.initials: U
authors.lastname: Ahmed
authors.forename: Annie
authors.initials: A
authors.lastname: Chou
authors.forename: Sylvia
authors.initials: S
authors.lastname: Sim
authors.forename: Daniel
authors.initials: D
authors.lastname: Carr
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murakami
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schleit
authors.forename: George L
authors.initials: GL
authors.lastname: Sutphin
authors.forename: Elroy H
authors.initials: EH
authors.lastname: An
authors.forename: Anthony
authors.initials: A
authors.lastname: Castanza
authors.forename: Marissa
authors.initials: M
authors.lastname: Fletcher
authors.forename: Sean
authors.initials: S
authors.lastname: Higgins
authors.forename: Monika
authors.initials: M
authors.lastname: Jelic
authors.forename: Shannon
authors.initials: S
authors.lastname: Klum
authors.forename: Brian
authors.initials: B
authors.lastname: Muller
authors.forename: Zhao J
authors.initials: ZJ
authors.lastname: Peng
authors.forename: Dilreet
authors.initials: D
authors.lastname: Rai
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ros
authors.forename: Minnie
authors.initials: M
authors.lastname: Singh
authors.forename: Helen V
authors.initials: HV
authors.lastname: Wende
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.forename: Matt
authors.initials: M
authors.lastname: Kaeberlein
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000367:Age Factors; D003600:Cytosol / Q000378:metabolism*; D008136:Longevity; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C090045:AFG3 protein, S cerevisiae