ArticleAging and disease2018
SIRT3 Protects Rotenone-induced Injury in SH-SY5Y Cells by Promoting Autophagy through the LKB1-AMPK-mTOR Pathway.
Article in Aging and disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 137 citations in OpenAlex.
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- Unveiling Exosomes and Microvesicles in Parkinson's Disease: Mechanistic Insights Into Cell Death Pathways and Therapeutic Potential.Molecular neurobiology · 2025Review
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- SIRT3-Mediated Deacetylation of DRP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
- [Lupeol Alleviates Chondrocytes Senescence in Osteoarthritis by Regulating Autophagy via the Sirtuin 3/Mechanistic Target of Rapamycin Kinase Pathway].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- The Protective Effect of Docosahexaenoic Acid on Mitochondria in SH-SY5Y Model of Rotenone-Induced Toxicity.Metabolites · 2025Article
- Dexmedetomidine reduces acute lung injury caused by LPS through the SIRT3 signaling pathwayFrontiers in pharmacology · 2025Article
- Z-Ligustilide: A Potential Therapeutic Agent for Atherosclerosis Complicating Cerebrovascular Disease.Biomolecules · 2024Review
- Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson's disease.Molecular biomedicine · 2024Article
- Advances in SIRT3 involvement in regulating autophagy-related mechanisms.Cell division · 2024Review
- Sirt3 Protects Retinal Pigment Epithelial Cells From High Glucose-Induced Injury by Promoting Mitophagy Through the AMPK/mTOR/ULK1 Pathway.Translational vision science & technology · 2024Article
- SIRT3 Activation a Promise in Drug Development? New Insights into SIRT3 Biology and Its Implications on the Drug Discovery Process.Journal of medicinal chemistry · 2024Review
- The underlying molecular mechanisms of Fyn in neonatal hypoxic-ischaemic encephalopathy.Frontiers in cellular neuroscience · 2024Review
- Targeting Mitochondrial Sirtuins in Age-Related Neurodegenerative Diseases and Fibrosis.Aging and disease · 2023Review
- Article
- LRRK2 Knockout Confers Resistance in HEK-293 Cells to Rotenone-Induced Oxidative Stress, Mitochondrial Damage, and Apoptosis.International journal of molecular sciences · 2023Article
- Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review).International journal of molecular medicine · 2023Review
- Sirtuin 3 regulation: a target to alleviate β-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells.Journal of animal science and biotechnology · 2023Article
- Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer's and Parkinson's diseases.Biology of sex differences · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
SIRT3 is a class III histone deacetylase that modulates energy metabolism, genomic stability and stress resistance. It has been implicated as a potential therapeutic target in a variety of neurodegenerative diseases, including Parkinson's disease (PD). Our previous study demonstrates that SIRT3 had a neuroprotective effect on a rotenone-induced PD cell model, however, the exact mechanism is unknown. In this study, we investigated the underlying mechanism. We established a SIRT3 stable overexpression cell line using lentivirus infection in SH-SY5Y cells. Then, a PD cell model was established using rotenone. Our data demonstrate that overexpression of SIRT3 increased the level of the autophagy markers LC3 II and Beclin 1. After addition of the autophagy inhibitor 3-MA, the protective effect of SIRT3 diminished: the cell viability decreased, while the apoptosis rate increased; α-synuclein accumulation enhanced; ROS production increased; antioxidants levels, including SOD and GSH, decreased; and MMP collapsed. These results reveal that SIRT3 has neuroprotective effects on a PD cell model by up-regulating autophagy. Furthermore, SIRT3 overexpression also promoted LKB1 phosphorylation, followed by activation of AMPK and decreased phosphorylation of mTOR. These results suggest that the LKB1-AMPK-mTOR pathway has a role in induction of autophagy. Together, our findings indicate a novel mechanism by which SIRT3 protects a rotenone-induced PD cell model through the regulation of autophagy, which, in part, is mediated by activation of the LKB1-AMPK-mTOR pathway.
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