ArticleNeurobiology of disease2014
Intramitochondrial Zn2+ accumulation via the Ca2+ uniporter contributes to acute ischemic neurodegeneration.
Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Knowledge mapping of mitochondrial calcium uniporter from 2011 to 2022: A bibliometric analysis.Frontiers in physiology · 2023Pooled it
- Post-ischemic inhibition of the mitochondrial Ca2+ uniporter with Ru265 protects in ex vivo and in vivo models of cerebral ischemia.Clinical science (London, England : 1979) · 2026Article
- Degradable STING nanomodulators orchestrate the innate-to-adaptive immune response for NIR-II photothermal-immunotherapy via a cancer-immunity cycle.Materials today. Bio · 2026Article
- Mechanisms of delayed ischemia/reperfusion evoked ROS generation in the hippocampal CA1 zone of adult mouse brain slices.Scientific reports · 2025Article
- Coordination of SLC39A1 and DRP1 facilitates HCC recurrence by impairing mitochondrial quality control.Clinical and translational medicine · 2025Article
- Recent research progress on metal ions and metal-based nanomaterials in tumor therapy.Frontiers in bioengineering and biotechnology · 2025Review
- Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- What Are the Functions of Zinc in the Nervous System?Neurology · 2023Article
- Expression of the HAntioxidants (Basel, Switzerland) · 2023Article
- Preserving and enhancing mitochondrial function after stroke to protect and repair the neurovascular unit: novel opportunities for nanoparticle-based drug delivery.Frontiers in cellular neuroscience · 2023Review
- A pair of transporters controls mitochondrial ZnProtein & cell · 2022Article
- HAntioxidants (Basel, Switzerland) · 2022Review
- Evolutionary rate covariation identifies SLC30A9 (ZnT9) as a mitochondrial zinc transporter.The Biochemical journal · 2021Article
- Mitochondrial Metal Ion Transport in Cell Metabolism and Disease.International journal of molecular sciences · 2021Review
- The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction.Biomedicines · 2021Review
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
- The role of labile ZnMolecular and cellular biochemistry · 2021Review
- Zinc cytotoxicity induces mitochondrial morphology changes in hela cell line.International journal of physiology, pathophysiology and pharmacology · 2021Article
- Combinatorial roles of mitochondria and cGMP/PKG pathway in the generation of neuronal free Zn2+ under the presence of nitric oxide.Journal of the Chinese Medical Association : JCMA · 2020Article
- ZnExperimental neurology · 2020Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Ca(2+) and Zn(2+) have both been implicated in the induction of acute ischemic neurodegeneration. We recently examined changes in intracellular Zn(2+) and Ca(2+) in CA1 pyramidal neurons subjected to oxygen glucose deprivation (OGD), and found that Zn(2+) rises precede and contribute to the onset of terminal Ca(2+) rises ("Ca(2+) deregulation"), which are causatively linked to a lethal loss of membrane integrity. The present study seeks to examine the specific role of intramitochondrial Zn(2+) accumulation in ischemic injury, using blockers of the mitochondrial Ca(2+) uniporter (MCU), through which both Zn(2+) and Ca(2+) appear able to enter the mitochondrial matrix. In physiological extracellular Ca(2+), treatment with the MCU blocker, Ruthenium Red (RR), accelerated the Ca(2+) deregulation, most likely by disrupting mitochondrial Ca(2+) buffering and thus accelerating the lethal cytosolic Ca(2+) overload. However, when intracellular Ca(2+) overload was slowed, either by adding blockers of major Ca(2+) entry channels or by lowering the concentration of Ca(2+) in the extracellular buffer, Ca(2+) deregulation was delayed, and under these conditions either Zn(2+) chelation or MCU blockade resulted in similar further delays of the Ca(2+) deregulation. In parallel studies using the reactive oxygen species (ROS) indicator, hydroethidine, lowering Ca(2+) surprisingly accelerated OGD induced ROS generation, and in these low Ca(2+) conditions, either Zn(2+) chelation or MCU block slowed the ROS generation. These studies suggest that, during acute ischemia, Zn(2+) entry into mitochondria via the MCU induces mitochondrial dysfunction (including ROS generation) that occurs upstream of, and contributes to the terminal Ca(2+) deregulation.
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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.