ArticleNature metabolism2021
The SESAME complex regulates cell senescence through the generation of acetyl-CoA.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
- Photo-downregulation of SIRT4 mitigates aging in mice by enhancing H3K9ac via fatty acid metabolism.eLife · 2026Article
- Host-Pathogen Interaction as a Driver of Cellular Senescence: Microbial Triggers and Host Response.International journal of molecular sciences · 2026Review
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- Lysine acetyltransferase 8-mediated histone acetylation, regulated by GBA1, is associated with lysosomal function related to α-Synuclein pathology.Cell death & disease · 2026Article
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- Cell Cycle Control of Nuclear Metabolism Couples Phosphatidylinositol Signaling to Histone Methylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Acetyl-CoA Synthetase 1 regulates global histone propionylation and metabolic stress responses.bioRxiv : the preprint server for biology · 2026Article
- Local acetyl-CoA metabolism and acetate recycling as epigenetic regulators of chromatin dynamics.FEMS yeast research · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- SREBP1-mediated lipogenesis promotes dedifferentiation and senescence of vascular smooth muscle cells through epigenetic remodeling.Nature communications · 2025Article
- Biomarkers of ageing of humans and non-human primates.Nature reviews. Molecular cell biology · 2025Review
- TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control.BMC biology · 2025Review
- ACSS2 coupled with KAT7 regulates histone β-hydroxybutyrylation to enhance transcription.Science advances · 2025Article
- Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Observational
- Mitochondrial dysfunction in the regulation of aging and aging-related diseases.Cell communication and signaling : CCS · 2025Review
- Candida auris cells form giant lipid droplets to survive in harsh environments.Communications biology · 2025Article
- PKA plays a conserved role in regulating gene expression and metabolic adaptation by phosphorylating Rpd3/HDAC1.Nature communications · 2025Article
- ACSS2 drives senescence-associated secretory phenotype by limiting purine biosynthesis through PAICS acetylation.Nature communications · 2025Article
- The Inhibitory Effects of NCT503 and Exogenous Serine on High-Selenium Induced Insulin Resistance in Mice.Nutrients · 2025Article
- Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Acetyl-CoA is a central node in carbon metabolism and plays critical roles in regulatory and biosynthetic processes. The acetyl-CoA synthetase Acs2, which catalyses acetyl-CoA production from acetate, is an integral subunit of the serine-responsive SAM-containing metabolic enzyme (SESAME) complex, but the precise function of Acs2 within the SESAME complex remains unclear. Here, using budding yeast, we show that Acs2 within the SESAME complex is required for the regulation of telomere silencing and cellular senescence. Mechanistically, the SESAME complex interacts with the histone acetyltransferase SAS protein complex to promote histone H4K16 acetylation (H4K16ac) enrichment and the occupancy of bromodomain-containing protein, Bdf1, at subtelomeric regions. This interaction maintains telomere silencing by antagonizing the spreading of Sir2 along the telomeres, which is enhanced by acetate. Consequently, dissociation of Sir2 from telomeres by acetate leads to compromised telomere silencing and accelerated chronological ageing. In human endothelial cells, ACSS2, the ortholog of yeast Acs2, also interacts with H4K16 acetyltransferase hMOF and are required for acetate to increase H4K16ac, reduce telomere silencing and induce cell senescence. Altogether, our results reveal a conserved mechanism to connect cell metabolism with telomere silencing and cellular senescence.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.