Epigenetic Silencing Mediates Mitochondria Stress-Induced Longevity

被引:155
作者
Schroeder, Elizabeth A. [1 ,2 ]
Raimundo, Nuno [1 ]
Shadel, Gerald S. [1 ,2 ]
机构
[1] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
关键词
INCREASING OXIDATIVE STRESS; CHRONOLOGICAL LIFE-SPAN; DNA-DAMAGE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; HISTONE H3; RAD53; KINASE; YEAST; TRANSCRIPTION; TELOMERES;
D O I
10.1016/j.cmet.2013.04.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Reactive oxygen species (ROS) play complex roles in aging, having both damaging effects and signaling functions. Transiently elevating mitochondrial stress, including mitochondrial ROS (mtROS), elicits beneficial responses that extend lifespan. However, these adaptive, longevity-signaling pathways remain poorly understood. We show here that Tel1p and Rad53p, homologs of the mammalian DNA damage response kinases ATM and Chk2, mediate a hormetic mtROS longevity signal that extends yeast chronological lifespan. This pathway senses mtROS in a manner distinct from the nuclear DNA damage response and ultimately imparts longevity by inactivating the histone demethylase Rph1p specifically at subtelomeric heterochromatin, enhancing binding of the silencing protein Sir3p, and repressing subtelomeric transcription. These results demonstrate the existence of conserved mitochondria-to-nucleus stress-signaling pathways that regulate aging through epigenetic modulation of nuclear gene expression.
引用
收藏
页码:954 / 964
页数:11
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