ArticleThe Journal of biological chemistry2013
A calcineurin docking motif (LXVP) in dynamin-related protein 1 contributes to mitochondrial fragmentation and ischemic neuronal injury.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- PI3K-Akt signaling network crosstalk in cerebral ischemia/reperfusion injury: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- A rule-based simulation model illuminates the role of asymmetric mitochondrial fission on beta-cell health.NPJ systems biology and applications · 2026Article
- Endoplasmic Reticulum-Mitochondrial Crosstalk in Calcium Regulation: Mechanistic Insights and Therapeutic Implications in Traumatic Brain Injury.Molecular neurobiology · 2026Review
- Mitochondrial calcium uniporter-mediated mitochondrial dynamics imbalance contributes to contrast medium-induced renal tubular cell injury.Frontiers in molecular biosciences · 2026Article
- A TRPM2-Driven Signalling Cycle Orchestrates Abnormal Inter-Organelle Crosstalk in Cardiovascular and Metabolic Diseases.Biomolecules · 2025Review
- Tacrolimus Improves Therapeutic Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Diabetic Retinopathy by Suppressing DRP1-Mediated Mitochondrial Fission.Antioxidants (Basel, Switzerland) · 2023Article
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Utilization of commercial collagens for preparing well-differentiated human beta cells for confocal microscopy.Frontiers in endocrinology · 2023Article
- Role of Takeda G protein‑coupled receptor 5 in microvascular endothelial cell dysfunction in diabetic retinopathy (Review).Experimental and therapeutic medicine · 2022Review
- Schizophrenia predisposition gene Unc-51-like kinase 4 for the improvement of cerebral ischemia/reperfusion injury.Molecular biology reports · 2022Article
- Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- Extract of Cynomorium songaricum ameliorates mitochondrial ultrastructure impairments and dysfunction in two different in vitro models of Alzheimer's disease.BMC complementary medicine and therapies · 2021Article
- Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.JCI insight · 2021Article
- Mitochondrial Fusion and Fission in Neuronal Death Induced by Cerebral Ischemia-Reperfusion and Its Clinical Application: A Mini-Review.Medical science monitor : international medical journal of experimental and clinical research · 2020Review
- Calcineurin-AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends.The Journal of physiology · 2020Review
- Mechanisms and roles of mitochondrial localisation and dynamics in neuronal function.Neuronal signaling · 2020Review
- Deletion of a Neuronal Drp1 Activator Protects against Cerebral Ischemia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- A novel peptide exerts potent immunosuppression by blocking the two-site interaction of NFAT with calcineurin.The Journal of biological chemistry · 2020Article
- Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury.Cells · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fission and fusion events dynamically control the shape and function of mitochondria. The activity of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1) is finely tuned by several post-translational modifications. Phosphorylation of Ser-656 by cAMP-dependent protein kinase (PKA) inhibits Drp1, whereas dephosphorylation by a mitochondrial protein phosphatase 2A isoform and the calcium-calmodulin-dependent phosphatase calcineurin (CaN) activates Drp1. Here, we identify a conserved CaN docking site on Drp1, an LXVP motif, which mediates the interaction between the phosphatase and mechanoenzyme. We mutated the LXVP motif in Drp1 to either increase or decrease similarity to the prototypical LXVP motif in the transcription factor NFAT, and assessed stability of the mutant Drp1-CaN complexes by affinity precipitation and isothermal titration calorimetry. Furthermore, we quantified effects of LXVP mutations on Drp1 dephosphorylation kinetics in vitro and in intact cells. With tools for bidirectional control of the CaN-Drp1 signaling axis in hand, we demonstrate that the Drp1 LXVP motif shapes mitochondria in neuronal and non-neuronal cells, and that CaN-mediated Drp1 dephosphorylation promotes neuronal death following oxygen-glucose deprivation. These results point to the CaN-Drp1 complex as a potential target for neuroprotective therapy of ischemic stroke.
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Registered trials
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