ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Sirtuin 5-mediated desuccinylation of PRDX6 inhibits ferroptosis and alleviates sepsis-associated acute kidney injury.Redox report : communications in free radical research · 2026Article
- SIRT7-mediated desuccinylation of FOXO4 suppresses ferroptosis to alleviate LPS-induced acute lung injury.Redox biology · 2026Article
- The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.Nature communications · 2026Article
- MicroRNA-SIRT1 crosstalk in liver diseases: molecular regulation of metabolism, inflammation, and cell survival.Molecular biology reports · 2026Review
- SIRT5-mediated HSDL2 desuccinylation promotes diabetic-associated cognitive dysfunction via disrupting mitochondrial TRAP1.Cell biology and toxicology · 2026Article
- Succinylation: A novel regulatory axis in cholelithiasis-insights from lysine acetyltransferase 2A/adenosine monophosphate-activated protein kinase signaling.World journal of gastroenterology · 2026Article
- TM9SF1 Aggravates Liver Ischemia-Reperfusion Injury by Promoting Autophagy.Inflammation · 2026Article
- Investigating Mitochondrial Viscosity in Ferroptosis-Mediated Drug-Induced Liver Injury using a Double-Targeted Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- Multi-omics analysis identifies a hepatocyte-associated signature in alcohol-related liver injury.Frontiers in immunology · 2026Article
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- [Role of succinylation modification in central nervous system diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- The Regulatory Role ofAntioxidants (Basel, Switzerland) · 2025Article
- Bioorthogonal Probe BTD-Az Enables Sensitive and Rapid In Vivo Profiling of Protein Cysteine Sulfenylation.Bioconjugate chemistry · 2025Article
- Explore sirtuin family: SIRT5 as a ticket for the entrance of the TBK1-RelA axis to skeletal muscle rejuvenation.Life medicine · 2025Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Mutation Spectrum ofInternational journal of molecular sciences · 2025Article
- Puerarin Improves Cancer-Induced Bone Pain by Recovering Mitochondrial Dysfunction in the Spinal Cord.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- SIRT5: a potential target for discovering bioactive natural products.Journal of natural medicines · 2025Review
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Authors and funding
15 authors.
Funding
Abstract
Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury. Sirtuins 5 (SIRT5) has been implicated in the development of various liver diseases. However, its involvement in APAP-induced acute liver injury (AILI) remains unclear. The present study aimed to explore the role of SIRT5 in AILI. SIRT5 expression is dramatically downregulated by APAP administration in mouse livers and AML12 hepatocytes. SIRT5 deficiency not only exacerbates liver injury and the inflammatory response, but also worsens mitochondrial oxidative stress. Conversely, the opposite pathological and biochemical changes are observed in mice with SIRT5 overexpression. Mechanistically, quantitative succinylome analysis and site mutation experiments revealed that SIRT5 desuccinylated aldehyde dehydrogenase 2 (ALDH2) at lysine 385 and maintained the enzymatic activity of ALDH2, resulting in the suppression of inflammation and mitochondrial oxidative stress. Furthermore, succinylation of ALDH2 at lysine 385 abolished its protective effect against AILI, and the protective effect of SIRT5 against AILI is dependent on the desuccinylation of ALDH2 at K385. Finally, virtual screening of natural compounds revealed that Puerarin promoted SIRT5 desuccinylase activity and further attenuated AILI. Collectively, the present study showed that the SIRT5-ALDH2 axis plays a critical role in AILI progression and might be a strategy for therapeutic intervention.
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