ArticleCell death and differentiation2016
The SR/ER-mitochondria calcium crosstalk is regulated by GSK3β during reperfusion injury.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Palmitic Acid Inhibits the Proliferation and Hypertrophy of Antler Chondrocytes by Disrupting Mitochondria-Associated Endoplasmic Reticulum Membrane Function.Antioxidants (Basel, Switzerland) · 2026Article
- Synthesis and Antitumor Mechanism of Emodin-Derived Transition Metal Complexes.Molecules (Basel, Switzerland) · 2026Article
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Organelle regulation of ferroptosis after intracerebral hemorrhage.Redox biology · 2026Review
- Huoxue Qianyang Qutan Recipe limits cardiac remodeling by regulating FUNDC1/IP3R2 signaling pathway in obese hypertensive rats.Scientific reports · 2026Article
- Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin.Antioxidants (Basel, Switzerland) · 2026Article
- Parkinson's disease-associated PLA2G6 protects IP3R1 protein to control ER-mitochondria tethering and CaNature communications · 2026Article
- The spatiotemporal dynamics of MAMs: mechanisms, pathologies, and therapeutic rewiring.Cellular & molecular biology letters · 2026Review
- Mitochondria-associated endoplasmic reticulum membranes: Emerging regulators of cardiac microvascular ischemia/reperfusion injury (Review).International journal of molecular medicine · 2026Review
- Dynamic imbalance of mitochondria-associated ER membranes in cardiovascular disease: mechanisms, context dependence and therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- The interaction between sarcoplasmic reticulum and mitochondria: a novel mechanism for cardiac arrhythmia.Frontiers in physiology · 2026Review
- Parkin Deficiency Impairs ER-Mitochondria Associations and calcium homeostasis via IP3R-Grp75-VDAC1 Complex.International journal of biological sciences · 2026Article
- MAMs-Mediated Calcium Homeostasis in the Pathophysiology of Cardiovascular Diseases: A Mini-Review.Drug design, development and therapy · 2026Review
- Cardiac SR-Mitochondria Contacts-Impact on Cardiac Physiology and Mitochondrial Fitness.Cells · 2025Review
- Phospholipase C epsilon 1 as a therapeutic target in cardiovascular diseases.Journal of advanced research · 2025Review
- Review
- Tea Polyphenol Modulates Mitochondria-Associated Endoplasmic Reticulum Membrane of Hippocampal Neurons Targeting Grp75 to Ameliorate Memory Impairment in the Aged T2DM Rats.Food science & nutrition · 2025Article
- Sarcoplasmic reticulum-mitochondria microdomains: hugging and kissing in the heart.American journal of physiology. Cell physiology · 2025Review
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycogen synthase kinase-3β (GSK3β) is a multifunctional kinase whose inhibition is known to limit myocardial ischemia-reperfusion injury. However, the mechanism mediating this beneficial effect still remains unclear. Mitochondria and sarco/endoplasmic reticulum (SR/ER) are key players in cell death signaling. Their involvement in myocardial ischemia-reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. We questioned here whether GSK3β might have a role in the Ca(2+) transfer from SR/ER to mitochondria at reperfusion. We showed that a fraction of GSK3β protein is localized to the SR/ER and mitochondria-associated ER membranes (MAMs) in the heart, and that GSK3β specifically interacted with the inositol 1,4,5-trisphosphate receptors (IP3Rs) Ca(2+) channeling complex in MAMs. We demonstrated that both pharmacological and genetic inhibition of GSK3β decreased protein interaction of IP3R with the Ca(2+) channeling complex, impaired SR/ER Ca(2+) release and reduced the histamine-stimulated Ca(2+) exchange between SR/ER and mitochondria in cardiomyocytes. During hypoxia reoxygenation, cell death is associated with an increase of GSK3β activity and IP3R phosphorylation, which leads to enhanced transfer of Ca(2+) from SR/ER to mitochondria. Inhibition of GSK3β at reperfusion reduced both IP3R phosphorylation and SR/ER Ca(2+) release, which consequently diminished both cytosolic and mitochondrial Ca(2+) concentrations, as well as sensitivity to apoptosis. We conclude that inhibition of GSK3β at reperfusion diminishes Ca(2+) leak from IP3R at MAMs in the heart, which limits both cytosolic and mitochondrial Ca(2+) overload and subsequent cell death.
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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.