ArticleEMBO reports2020
Acetyltransferase GCN5 regulates autophagy and lysosome biogenesis by targeting TFEB.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 142 citations in OpenAlex.
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- Crotonylation of ACAT1 K181 contributes to radioresistance by impacting lactate metabolism.Communications biology · 2026Article
- Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets.Journal of pharmaceutical analysis · 2026Article
- Acetylation of STX17 promotes its autophagosomal translocation.Nature communications · 2026Article
- Deficiency of GCN5 exacerbates pulmonary fibrosis by disrupting the LKB1-AMPK pathway.Cell communication and signaling : CCS · 2026Article
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Article
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- Cadmium targeting transcription factor EB to inhibit autophagy-lysosome function contributes to acute kidney injury.Journal of advanced research · 2025Article
- Yeast cells experience chronological life span extension under prolonged glucose starvation.Heliyon · 2025Article
- Evolutionary conserved regulation of TFEB stability by the E3 ubiquitin ligase WWP2 modulates response to stressiScience · 2025Article
- The advances in acetylation modification in senescence and aging-related diseases.Frontiers in physiology · 2025Review
- Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown inMetabolites · 2024Article
- Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity.The Journal of cell biology · 2024Article
- Regulation of Caenorhabditis elegans HLH-30 subcellular localization dynamics: Evidence for a redox-dependent mechanism.Free radical biology & medicine · 2024Article
- LINC00887 promotes GCN5-dependent H3K27cr level and CRC metastasis via recruitment of YEATS2 and enhancing ETS1 expression.Cell death & disease · 2024Article
- Myeloid-specific Hdac10 deletion protects against LPS-induced acute lung injury via P62 acetylation at lysine 165.Respiratory research · 2024Article
- Acetylation modification in the regulation of macroautophagy.Advanced biotechnology · 2024Review
- GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.British journal of cancer · 2024Article
- Autophagy, a double-edged sword for oral tissue regeneration.Journal of advanced research · 2024Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Accumulating evidence highlights the role of histone acetyltransferase GCN5 in the regulation of cell metabolism in metazoans. Here, we report that GCN5 is a negative regulator of autophagy, a lysosome-dependent catabolic mechanism. In animal cells and Drosophila, GCN5 inhibits the biogenesis of autophagosomes and lysosomes by targeting TFEB, the master transcription factor for autophagy- and lysosome-related gene expression. We show that GCN5 is a specific TFEB acetyltransferase, and acetylation by GCN5 results in the decrease in TFEB transcriptional activity. Induction of autophagy inactivates GCN5, accompanied by reduced TFEB acetylation and increased lysosome formation. We further demonstrate that acetylation at K274 and K279 disrupts the dimerization of TFEB and the binding of TFEB to its target gene promoters. In a Tau-based neurodegenerative Drosophila model, deletion of dGcn5 improves the clearance of Tau protein aggregates and ameliorates the neurodegenerative phenotypes. Together, our results reveal GCN5 as a novel conserved TFEB regulator, and the regulatory mechanisms may be involved in autophagy- and lysosome-related physiological and pathological processes.
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Registered trials
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.