ArticleRedox biology2018
Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis that pooled it.
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Who cites it
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 349 citations in OpenAlex.
- Inappropriate Diet Exacerbates Metabolic Dysfunction-Associated Steatotic Liver Disease via Abdominal Obesity.Nutrients · 2024Pooled it
- Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets.Annals of medicine · 2026Review
- Mitophagy in Metabolic Dysfunction-Associated Fatty Liver Disease: Mechanisms, Regulatory Networks, and Therapeutic Perspectives.Inflammation · 2026Review
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- The SIRT3-DsbA-L-TFAM axis restrains cGAS-driven metabolic dysfunction-associated steatohepatitis in male mice.Nature communications · 2026Article
- Targeting the Gut-Liver Mitochondria Axis in MASLD: Mechanisms and Therapeutic Perspectives.Current medical science · 2026Review
- Association of HIF1α, BNIP3, and BNIP3L with Hypoxia-Related Metabolic Stress in Metabolic Syndrome.Medicina (Kaunas, Lithuania) · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Relevance and application of sirtuin 3-activated mitophagy in gastric cancer treatment.World journal of clinical oncology · 2025Review
- Fat-targeted small molecule alleviates abnormal adipose tissue remodeling in obesity via SIRT3-driven mitophagy and inflammasome inhibition.Chinese medicine · 2025Article
- R-spondin 2 suppresses hepatic steatosis via activation of AMPK-ACC signaling.JHEP reports : innovation in hepatology · 2025Article
- Sirtuins in mitophagy: key gatekeepers of mitochondrial quality.Molecular and cellular biochemistry · 2025Review
- Cell-specific roles of autophagy in liver fibrosis: implications for targeted pharmacotherapy.Annals of medicine · 2025Review
- A novel strategy for the protective effect of ginsenoside Rg1 against ovarian reserve decline by the PINK1 pathway.Pharmaceutical biology · 2025Article
- Mitochondrial Quality Control and Cell Death.International journal of molecular sciences · 2025Review
- Ginsenoside CK potentiates SIRT1 to alleviate lupus nephritis through compensating for XBP1-mediated endoplasmic reticulum stress in plasma cells.Journal of pharmaceutical analysis · 2025Article
- Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025Review
- SIRT3 Acetylation Regulates Mitophagy to Alleviate Deoxynivalenol-Induced Apoptosis in Porcine Alveolar Macrophages Cells.International journal of molecular sciences · 2025Article
- Disrupted host-microbiota crosstalk promotes nonalcoholic fatty liver disease progression by impaired mitophagy.Microbiology spectrum · 2025Article
- Sirtuin-3 promotes osteoclast maturation and bone loss by regulating mitochondrial ROS production during ionizing radiation exposure.JBMR plus · 2025Article
125 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased mitochondrial damage is related to the progression of a diet-induced nonalcoholic fatty liver disease. The aim of our study is to investigate the role of Sirtuin 3 (Sirt3) in treating nonalcoholic fatty liver disease with a focus on mitophagy and the ERK-CREB pathway. Our data indicated that Sirt3 was downregulated in liver tissue in response to chronic HFD treatment. Interestingly, re-introduction of Sirt3 protected hepatic function, attenuated liver fibrosis, alleviated the inflammatory response, and prevented hepatocyte apoptosis. Molecular investigations demonstrated that lipotoxicity was associated with an increase in mitochondrial apoptosis as evidenced by reduced mitochondrial potential, augmented ROS production, increased cyt-c leakage into the nucleus, and activated caspase-9 apoptotic signalling. Additionally, Sirt3 overexpression protected hepatocytes against mitochondrial apoptosis via promoting Bnip3-required mitophagy. Functional studies showed that Sirt3 reversed Bnip3 expression and mitophagy activity via the ERK-CREB signalling pathway. Blockade of the ERK-CREB axis repressed the promotive effects of Sirt3 on Bnip3 activation and mitophagy augmentation, finally negating the anti-apoptotic influences of Sirt3 on hepatocytes in the setting of high-fat-stress. Collectively, our data show that high-fat-mediated liver damage is associated with Sirt3 downregulation, which is followed by ERK-CREB pathway inactivation and Bnip3-mediated inhibition of mitophagy, causing hepatocytes to undergo mitochondria-dependent cell death. Based on this, strategies for enhancing Sirt3 activity and activating the ERK-CREB-Bnip3-mitophagy pathways could be used to treat nonalcoholic fatty liver disease.
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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.