Epigenetic Silencing Mediates Mitochondria Stress-Induced Longevity
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 r...
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Veröffentlicht in: | Cell metabolism 2013-06, Vol.17 (6), p.954-964 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•The H3K36 demethylase Rph1p is required for mitochondrial stress-induced longevity•Conserved DNA damage response kinases transduce mitochondrial ROS signals•Mitochondria ROS signals reduce Rph1p binding at subtelomeres and increase H3K36me3•Subtelomeric silencing is essential for mitochondrial ROS-mediated longevity |
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ISSN: | 1550-4131 1932-7420 |
DOI: | 10.1016/j.cmet.2013.04.003 |