ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Deciphering of mitochondrial cardiolipin oxidative signaling in cerebral ischemia-reperfusion.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 61 citations in OpenAlex.
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- Narrative review of rationale for IV deferoxamine plus intranasal insulin to ameliorate brain damage following resuscitation from cardiac arrest.Resuscitation plus · 2026Review
- Bridging the gap: Acute amantadine augments the neurorehabilitative efficacy of delayed and abbreviated environmental enrichment in a pediatric traumatic brain injury model.Brain research · 2026Article
- Mitochondrial dysfunction in intracerebral hemorrhage: molecular mechanisms and pathological consequences.Frontiers in cellular neuroscience · 2026Review
- The Role of Cardiolipin in Brain Bioenergetics, Neuroinflammation, and Neurodegeneration.Molecular neurobiology · 2025Review
- Nitroxides: Chemistry, Antioxidant Properties, and Biomedical Applications.Molecules (Basel, Switzerland) · 2025Review
- Special Issue "New Molecular Insights into Ischemia/Reperfusion".International journal of molecular sciences · 2024Article
- Ginsenoside Rg3 Restores Mitochondrial Cardiolipin Homeostasis via GRB2 to Prevent Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitigation of Fetal Radiation Injury from Mid-Gestation Total-body Irradiation by Maternal Administration of Mitochondrial-Targeted GS-Nitroxide JP4-039.Radiation research · 2024Article
- In Vitro Hypoxia/Reoxygenation Induces Mitochondrial Cardiolipin Remodeling in Human Kidney Cells.International journal of molecular sciences · 2024Article
- Unraveling the mechanisms of cardiolipin function: The role of oxidative polymerization of unsaturated acyl chains.Redox biology · 2023Article
- Restoring mitochondrial cardiolipin homeostasis reduces cell death and promotes recovery after spinal cord injury.Cell death & disease · 2022Article
- Advances in methods to analyse cardiolipin and their clinical applications.Trends in analytical chemistry : TRAC · 2022Article
- GLS2 Is a Tumor Suppressor and a Regulator of Ferroptosis in Hepatocellular Carcinoma.Cancer research · 2022Article
- Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review).International journal of molecular medicine · 2022Review
- Redox Pioneer: Professor Valerian Kagan.Antioxidants & redox signaling · 2022Article
- Association Between L-OPA1 Cleavage and Cardiac Dysfunction During Ischemia-Reperfusion Injury in Rats.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2020Article
- CRISPR/Cas9-mediated whole genomic wide knockout screening identifies mitochondrial ribosomal proteins involving in oxygen-glucose deprivation/reperfusion resistance.Journal of cellular and molecular medicine · 2020Article
- Monolysocardiolipin (MLCL) interactions with mitochondrial membrane proteins.Biochemical Society transactions · 2020Review
- Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protectsThe Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
It is believed that biosynthesis of lipid mediators in the central nervous system after cerebral ischemia-reperfusion starts with phospholipid hydrolysis by calcium-dependent phospholipases and is followed by oxygenation of released fatty acids (FAs). Here, we report an alternative pathway whereby cereberal ischemia-reperfusion triggered oxygenation of a mitochondria-specific phospholipid, cardiolipin (CL), is followed by its hydrolysis to yield monolyso-CLs and oxygenated derivatives of fatty (linoleic) acids. We used a model of global cerebral ischemia-reperfusion characterized by 9 minutes of asphyxia leading to asystole followed by cardiopulmonary resuscitation in postnatal day 17 rats. Global ischemia and cardiopulmonary resuscitation resulted in: (1) selective oxidation and hydrolysis of CLs, (2) accumulation of lyso-CLs and oxygenated free FAs, (3) activation of caspase 3/7 in the brain, and (4) motor and cognitive dysfunction. On the basis of these findings, we used a mitochondria targeted nitroxide electron scavenger, which prevented CL oxidation and subsequent hydrolysis, attenuated caspase activation, and improved neurocognitive outcome when administered after cardiac arrest. These data show that calcium-independent CL oxidation and subsequent hydrolysis represent a previously unidentified pathogenic mechanism of brain injury incurred by ischemia-reperfusion and a clinically relevant therapeutic target.
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Registered trials
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