Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging.

Authors: Delaney1 2 JR; Ahmed U; Chou A; Sim S; Carr D; Murakami CJ; Schleit J; Sutphin GL; An EH; Castanza A; Fletcher M; Higgins S; Jelic M; Klum S; Muller B; Peng ZJ; Rai D; Ros V; Singh M; Wende HV; Kennedy BK; Kaeberlein M
Year: 2012
Journal: Aging cell
Abstract: While environmental stress likely plays a significant role in promoting aging, the relationship remains poorly understood. In order 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, afg3 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 life span extension. These data demonstrate an unexpected link between a mitochondrial protease, cytoplasmic mRNA translation, and aging. (c) 2012 The Authors Aging Cell (c) 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.


Created on Nov. 22, 2012, 11:46 a.m.
Not linked
Integrated: False

No notes
Species: Budding yeast

Experiments: 6
  • Figure 5: Hac1-independent resistance to tunicamycin in afg3∆ and rpl20bΔ cells
  • Figure 6: Deletion of AFG3 reduces cytoplasmic translation and extends life span by a Sir2-independent, Gcn4-dependent mechanism
  • Supplemental Figure 2: Replicative lifespan curves of control strains sensitive to the tested stresses
  • Supplemental Figure 3: Growth curves and lifespan curves of respiratory dead or deficient strains
  • Supplemental Figure 4: Unsuppressed growth of afg3∆, yta12∆, and mrpl32∆ and corresponding lifespan curves
  • Supplemental Figure 5: Cold incubation similarly impairs afg3∆ cell growth and longevity relative to rpl20b∆ cells

  • Interventions:
  • IDH2 deletion
  • HAC1 deletion

  • Edit study (Admin) | Add experiment to study (Admin) | Delete study

    Comment on This Data Unit