ArticleThe Journal of biological chemistry2016
SIRT3 Deacetylates Ceramide Synthases: IMPLICATIONS FOR MITOCHONDRIAL DYSFUNCTION AND BRAIN INJURY.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 84 citations in OpenAlex.
- CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.The Biochemical journal · 2026Review
- Impact of Oxidized Phospholipids on Outcomes from Cerebral Ischemia and Reperfusion Injury.Pharmaceutics · 2026Article
- Therapeutic remodeling of the ceramide backbone prevents kidney injury.Cell metabolism · 2026Article
- Role of borneol as enhancer in drug formulation: A review.Chinese herbal medicines · 2025Review
- The advances in acetylation modification in senescence and aging-related diseases.Frontiers in physiology · 2025Review
- Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.Frontiers in neuroscience · 2025Review
- Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms.Current drug targets · 2025Review
- Environmental Temperature Variation Affects Brain Lipid Composition in Adult Zebrafish (International journal of molecular sciences · 2024Article
- Lipidomic analysis identifies long-chain acylcarnitine as a target for ischemic stroke.Journal of advanced research · 2024Article
- The role of SIRT3 in homeostasis and cellular health.Frontiers in cellular neuroscience · 2024Review
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- Role of NADCellular and molecular neurobiology · 2023Review
- Ceramide in cerebrovascular diseases.Frontiers in cellular neuroscience · 2023Review
- Role of SIRT3 in neurological diseases and rehabilitation training.Metabolic brain disease · 2023Review
- Sirtuin-3: A potential target for treating several types of brain injury.Frontiers in cell and developmental biology · 2023Review
- Sphingolipids in mitochondria-from function to disease.Frontiers in cell and developmental biology · 2023Review
- [Effects of Long-Term Ethanol Consumption on Learning-Memory Functions in Mice and the Mechanisms Involved].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Article
- Mitochondrial Sirtuins in Parkinson's Disease.Neurochemical research · 2022Review
- Oxygen-Glucose Deprivation/Reperfusion-Induced Sirt3 Reduction Facilitated Neuronal Injuries in an Apoptosis-Dependent Manner During Prolonged Reperfusion.Neurochemical research · 2022Article
- Involvement of Ceramide Metabolism in Cerebral Ischemia.Frontiers in molecular biosciences · 2022Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Experimental evidence supports the role of mitochondrial ceramide accumulation as a cause of mitochondrial dysfunction and brain injury after stroke. Herein, we report that SIRT3 regulates mitochondrial ceramide biosynthesis via deacetylation of ceramide synthase (CerS) 1, 2, and 6. Reciprocal immunoprecipitation experiments revealed that CerS1, CerS2, and CerS6, but not CerS4, are associated with SIRT3 in cerebral mitochondria. Furthermore, CerS1, -2, and -6 are hyperacetylated in the mitochondria of SIRT3-null mice, and SIRT3 directly deacetylates the ceramide synthases in a NAD(+)-dependent manner that increases enzyme activity. Investigation of the SIRT3 role in mitochondrial response to brain ischemia/reperfusion (IR) showed that SIRT3-mediated deacetylation of ceramide synthases increased enzyme activity and ceramide accumulation after IR. Functional studies demonstrated that absence of SIRT3 rescued the IR-induced blockade of the electron transport chain at the level of complex III, attenuated mitochondrial outer membrane permeabilization, and decreased reactive oxygen species generation and protein carbonyls in mitochondria. Importantly, Sirt3 gene ablation reduced the brain injury after IR. These data support the hypothesis that IR triggers SIRT3-dependent deacetylation of ceramide synthases and the elevation of ceramide, which could inhibit complex III, leading to increased reactive oxygen species generation and brain injury. The results of these studies highlight a novel mechanism of SIRT3 involvement in modulating mitochondrial ceramide biosynthesis and suggest an important role of SIRT3 in mitochondrial dysfunction and brain injury after experimental stroke.
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