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

Aging Cell

Joe R. Delaney²  Umema Ahmed²  Annie Chou²  Sylvia Sim²  Daniel Carr²  Christopher J. Murakami²  Jennifer Schleit²  George L. Sutphin²  Elroy H. An²  Anthony Castanza²  Marissa Fletcher²  Sean Higgins²  Monika Jelic²  Shannon Klum²  Brian Muller²  Zhao J. Peng²  Dilreet Rai²  Vanessa Ros²  Minnie Singh²  Helen V. Wende²  Brian K. Kennedy¹ 

[1] Buck Institute for Age Research, Novato, CA, USA;Department of Pathology, University of Washington, Seattle, WA, USA

关键词: aging;    epistasis;    ER stress;    longevity;    mitochondria;    phenotype mapping;    replicative lifespan;    stress response;    translation;    yeast;   

DOI  :  10.1111/acel.12032

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

Unknown   
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland