Epigenetic silencing mediates mitochondria stress-induced longevity
Open accessAbstract
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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ROS signals from mitochondria can affect chromatin-mediated silencing in yeast.
“ROS signals from the mitochondria can also impact chromatin-mediated silencing in yeast (Schroeder et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Schroeder et al., 2013
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- Authors
- Schroeder, E. A., Raimundo, N., & Shadel, G. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Shadel, Gerald S.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 17
- Issue
- 6
- Pages
- 954-964
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3694503
- OpenAlex
- W1998852095
- Cited by
- 186
- References
- 79
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 9 · 2022: 6 · 2021: 11 · 2020: 17 · 2019: 15 · 2018: 18 · 2017: 12 · 2016: 21 · 2015: 26 · 2014: 30 · 2013: 6
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Army Research Office
- United Mitochondrial Disease Foundation
- National Institutes of Health (T32 GM07499, F31 AG043242)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial stress, mitochondrial reactive oxygen species, longevity, aging, chronological lifespan, histone demethylation, Sir3p, heterochromatin, epigenetic silencing, hormesis, Saccharomyces cerevisiae
- MeSH terms
- DNA Damage, DNA Repair, Longevity, Mitochondria, Protein Binding, Repressor Proteins, Saccharomyces cerevisiae, Signal Transduction, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Cell Cycle Proteins, Gene Silencing, Saccharomyces cerevisiae Proteins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Intracellular Signaling Peptides and Proteins, Histone Demethylases, Epigenomics, Checkpoint Kinase 2
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