Stress profiling of longevity mutants identifies Afg3 as a mitochondrial determinant of cytoplasmic mRNA translation and aging
| Autor: | Annie Chou, George L. Sutphin, Elroy H. An, Joe R. Delaney, Brian Muller, Umema Ahmed, Dilreet Rai, Sylvia Sim, Sean Higgins, Minnie Singh, Marissa Fletcher, Jennifer Schleit, Anthony S. Castanza, Zhao J. Peng, Helen Vander Wende, Daniel B. Carr, Brian K. Kennedy, Matt Kaeberlein, Shannon Klum, Christopher J. Murakami, Monika Jelic, Vanessa Ros |
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| Rok vydání: | 2012 |
| Předmět: |
Aging
Saccharomyces cerevisiae Proteins Longevity Mutant Saccharomyces cerevisiae Mitochondrion Biology Article chemistry.chemical_compound Cytosol Ribosomal protein Protein biosynthesis RNA Messenger Gene Adenosine Triphosphatases Age Factors Translation (biology) Cell Biology Tunicamycin Molecular biology Mitochondria Cell biology chemistry Protein Biosynthesis Unfolded protein response Signal Transduction |
| Zdroj: | Aging Cell. 12:156-166 |
| ISSN: | 1474-9718 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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