ArticleAntioxidants & redox signaling2016
PGC-1α/ERRα-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly Deacetylating SOD2 and ATP Synthase β.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 129 citations in OpenAlex.
- Review
- Alisol A Mitigates Neuroinflammation and Oxidative Stress After Subarachnoid Hemorrhage Through SIRT3-Driven Reprogramming of Mitochondrial Metabolism.Molecular neurobiology · 2026Article
- Role of SIRT3 in digestive system diseases and therapeutic prospects (Review).International journal of molecular medicine · 2026Review
- The hidden driver of osteoporosis: mitochondria-dominated inflammation.Cell communication and signaling : CCS · 2025Review
- Mitochondria-driven inflammation: a new frontier in ovarian ageing.Journal of translational medicine · 2025Review
- Deficient AMPK-SENP1-Sirt3 signaling impairs mitochondrial complex I function in Parkinson's disease model.Translational neurodegeneration · 2025Article
- New Perspectives on Postmenopausal Osteoporosis: Mechanisms and Potential Therapeutic Strategies of Sirtuins and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Review
- SIRT3-Mediated Deacetylation of DRP1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- THRA1/PGC-1α/SIRT3 pathway regulates oxidative stress and is implicated in hypertension of maternal hypothyroid rat offspring.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- The mechanism and therapeutic potential of SIRT3 in central nervous system diseases: a review.Frontiers in pharmacology · 2025Review
- The Role of Sirtuins in Diabetic Nephropathy: A Comprehensive Review.Current protein & peptide science · 2025Review
- Mitochondrion-based organellar therapies for central nervous system diseases.Cell communication and signaling : CCS · 2024Review
- Estrogen related receptor alpha: Potential modulator of age-related macular degeneration.Current opinion in pharmacology · 2024Review
- Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.Cell death & disease · 2024Article
- The role of SIRT3 in homeostasis and cellular health.Frontiers in cellular neuroscience · 2024Review
- Mechanism and treatment of intracerebral hemorrhage focus on mitochondrial permeability transition pore.Frontiers in molecular neuroscience · 2024Review
- Article
- Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- HIV-1 Tat Induces Dysregulation of PGC1-Alpha and Sirtuin 3 Expression in Neurons: The Role of Mitochondrial Biogenesis in HIV-Associated Neurocognitive Disorder (HAND).International journal of molecular sciences · 2023Article
- Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer.Journal of translational medicine · 2023Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsParkinson's disease (PD) heavily affects humans and little is known about its cause and pathogenesis. Sirtuin 3 (Sirt3) plays a key role in regulating mitochondrial dysfunction, which is the main cause of DAergic neuronal loss in PD. We investigated the mechanisms of neuroprotective role of Sirt3 in DAergic neuronal survival.
resultsSirt3 was reduced in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated neurons with its overexpression being neuroprotective. We identified that Sirt3 interacted with manganese superoxide dismutase (SOD2) and adenosine triphosphate (ATP) synthase β and modulated their activities by deacetylating SOD2 (K130) and ATP synthase β (K485) to prevent reactive oxygen species accumulation and ATP depletion, and to alleviate DAergic neuronal death upon MPTP treatment. Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) interacted with estrogen-related receptor alpha (ERRα) that bound to the Sirt3 promoter as its transcription factor to regulate Sirt3 expression and DAergic neuronal death. In the mouse midbrain, MPTP administration led to the loss of PGC-1α and Sirt3, high acetylation level of SOD2 and ATP synthase β, and the specific loss of DAergic neurons, while Sirt3 overexpression could protect against DAergic neuronal loss. Sirt3 knockout mice exhibited more sensitive and more DAergic neuronal loss to MPTP treatment. INNOVATION: The study provides new insights into a critical PGC-1α/ERRα-Sirt3 pathway, linking regulation of mitochondrial protein acetylation and DAergic neuronal death in PD pathogenesis, which provide a potential therapeutic strategy and target in PD treatment.
conclusionThese results provide a vital PGC-1α/ERRα-Sirt3 pathway that protects against DAergic neuronal death by directly deacetylating SOD2 (K130) and ATP synthase β (K485) in PD.
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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.