Mitochondrial stress induces chromatin reorganization to promote longevity and UPR(mt)
Open accessAbstract
Organisms respond to mitochondrial stress through the upregulation of an array of protective genes, often perpetuating an early response to metabolic dysfunction across a lifetime. We find that mitochondrial stress causes widespread changes in chromatin structure through histone H3K9 di-methylation marks traditionally associated with gene silencing. Mitochondrial stress response activation requires the di-methylation of histone H3K9 through the activity of the histone methyltransferase met-2 and the nuclear co-factor lin-65. While globally the chromatin becomes silenced by these marks, remaining portions of the chromatin open up, at which point the binding of canonical stress responsive factors such as DVE-1 occurs. Thus, a metabolic stress response is established and propagated into adulthood of animals through specific epigenetic modifications that allow for selective gene expression and lifespan extension.
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H3K9 and H3K27 methylation changes are important for UPRmt gene induction in C. elegans, mice, and human cells.
“changes in the methylation of H3K9 and H3K27 have recently been found to be important for the induction of genes involved in the UPRmt in C. elegans, mice, and human cells (Merkwirth et al., 2016; Tian et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Tian et al., 2016
Global chromatin repression is important for specific upregulation of mitochondrial stress-response genes and lifespan extension.
“This global repression of chromatin is important to allow the specific upregulation of mitochondrial stress-response genes and lifespan extension (Tian et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Tian et al., 2016
In C. elegans, mitochondrial dysfunction causes increased H3K9 methylation and global chromatin compaction.
“in C. elegans, mitochondrial dysfunction results in increased H3K9 methylation and global compaction of chromatin.”
From The Aging Epigenome (2016) · cites this paper as Tian et al., 2016
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- Authors
- Tian, Y., Garcia, G., Bian, Q., Steffen, K. K., Joe, L., Wolff, S., Meyer, B. J., & Dillin, A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Dillin, Andrew
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 165
- Issue
- 5
- Pages
- 1197-1208
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4889216
- OpenAlex
- W2343051572
- Cited by
- 370
- References
- 43
- Citations by year
- 2026: 40 · 2025: 27 · 2024: 36 · 2023: 25 · 2022: 47 · 2021: 40 · 2020: 39 · 2019: 33 · 2018: 37 · 2017: 34 · 2016: 12
- FWCI
- 20.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5r01gm030702-36)
- National Institute on Aging (R37AG024365)
- National Institute of General Medical Sciences (R01-GM030702)
- National Center for Research Resources (S10RR029668, S10RR027303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- mitochondrial stress, chromatin reorganization, MET-2, longevity, lifespan extension, epigenetic regulation, gene silencing, Caenorhabditis elegans, metabolic stress response
- MeSH terms
- Animals, Gene Expression Regulation, Histones, Longevity, Mitochondria, Histone-Lysine N-Methyltransferase, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Unfolded Protein Response
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