ArticleThe Journal of biological chemistry2015
MFN2 couples glutamate excitotoxicity and mitochondrial dysfunction in motor neurons.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 103 citations in OpenAlex.
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- Cognitive impairment following maternal separation in rats mediated by the NADTranslational psychiatry · 2025Article
- Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration.International journal of molecular sciences · 2024Review
- Sulbactam protects neurons against double neurotoxicity of amyloid beta and glutamate load by upregulating glial glutamate transporter 1.Cell death discovery · 2024Article
- Diosgenin derivative ML5 attenuates MPTP-induced neuronal impairment via regulating AMPK/PGC-1α-mediated mitochondrial biogenesis and fusion/fission.American journal of translational research · 2024Article
- Targeted Treatment Strategies for Mitochondria Dysfunction: Correlation with Neurological Disorders.Current drug targets · 2024Review
- Photobiomodulation reduces neuropathic pain after spinal cord injury by downregulating CXCL10 expression.CNS neuroscience & therapeutics · 2023Article
- DNA Methylation-Mediated Mfn2 Gene Regulation in the Brain: A Role in Brain Trauma-Induced Mitochondrial Dysfunction and Memory Deficits.Cellular and molecular neurobiology · 2023Article
- Cell-Type-Specific Mitochondrial Quality Control in the Brain: A Plausible Mechanism of Neurodegeneration.International journal of molecular sciences · 2023Review
- Matrix metalloproteinase-2 proteolyzes mitofusin-2 and impairs mitochondrial function during myocardial ischemia-reperfusion injury.Basic research in cardiology · 2023Article
- N-Terminomic Changes in Neurons During Excitotoxicity Reveal Proteolytic Events Associated With Synaptic Dysfunctions and Potential Targets for Neuroprotection.Molecular & cellular proteomics : MCP · 2023Article
- Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age.Communications biology · 2023Article
- Mitofusin-2 mediates cannabidiol-induced neuroprotection against cerebral ischemia in rats.Acta pharmacologica Sinica · 2023Article
- Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review.Brain sciences · 2022Review
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- BrainPhys Neuronal Media Support Physiological Function of Mitochondria in Mouse Primary Neuronal Cultures.Frontiers in molecular neuroscience · 2022Article
- Mitophagy in neurological disorders.Journal of neuroinflammation · 2021Review
- Cerebellar White Matter Abnormalities in Charcot-Marie-Tooth Disease: A Combined Volumetry and Diffusion Tensor Imaging Analysis.Journal of clinical medicine · 2021Article
- Translational regulation in the brain by TDP-43 phase separation.The Journal of cell biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial dysfunction plays a central role in glutamate-evoked neuronal excitotoxicity, and mitochondrial fission/fusion dynamics are essential for mitochondrial morphology and function. Here, we establish a novel mechanistic linker among glutamate excitotoxicity, mitochondrial dynamics, and mitochondrial dysfunction in spinal cord motor neurons. Ca(2+)-dependent activation of the cysteine protease calpain in response to glutamate results in the degradation of a key mitochondrial outer membrane fusion regulator, mitofusin 2 (MFN2), and leads to MFN2-mediated mitochondrial fragmentation preceding glutamate-induced neuronal death. MFN2 deficiency impairs mitochondrial function, induces motor neuronal death, and renders motor neurons vulnerable to glutamate excitotoxicity. Conversely, MFN2 overexpression blocks glutamate-induced mitochondrial fragmentation, mitochondrial dysfunction, and/or neuronal death in spinal cord motor neurons both in vitro and in mice. The inhibition of calpain activation also alleviates glutamate-induced excitotoxicity of mitochondria and neurons. Overall, these results suggest that glutamate excitotoxicity causes mitochondrial dysfunction by impairing mitochondrial dynamics via calpain-mediated MFN2 degradation in motor neurons and thus present a molecular mechanism coupling glutamate excitotoxicity and mitochondrial dysfunction.
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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.