ArticleThe EMBO journal2014
Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 101 citations in OpenAlex.
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- [Deubiquitinase USP30 alleviates brain injury after intracerebral hemorrhage by regulating MFN2 ubiquitination].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Astrocytic Mitochondria Transplantation Rescues Neuron Loss and Dendritic Injuries in Acute Cerebral Ischemic Stroke Mouse Model by Flexibly Regulating Mitochondria Dynamics.Annals of neurology · 2026Article
- The role of mitochondria-associated membranes in tumorigenesis.Discover oncology · 2026Review
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- Tubular ER dysfunction in neurodegenerative diseases.Neurobiology of disease · 2025Review
- Charcot-Marie-Tooth type 2A variants of mitofusin 2 sensitize cells to apoptotic cell death.Journal of cell science · 2025Article
- p-Coumaric acid alleviates neuronal damage in ischemic stroke mice by promoting BACH1 nuclear export and degradation.Acta pharmacologica Sinica · 2025Article
- Mitochondrial dynamics in diabetic peripheral neuropathy: Pathogenesis, progression, and therapeutic approaches.Medicine · 2025Review
- Mitofusin 2 Mediates the Protective Effect of NR6A1 Silencing Against Neuronal Injury in Experimental Stroke Models.Molecular neurobiology · 2025Article
- KNTC1 introduces segmental heterogeneity to mitochondria.Disease models & mechanisms · 2025Article
- CLEC16A in astrocytes promotes mitophagy and limits pathology in a multiple sclerosis mouse model.Nature neuroscience · 2025Article
- BI1 Activates Autophagy and Mediates TDP43 to Regulate ALS Pathogenesis.Molecular neurobiology · 2025Article
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- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- MAM-mediated mitophagy and endoplasmic reticulum stress: the hidden regulators of ischemic stroke.Frontiers in cellular neuroscience · 2024Review
- Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma.International journal of biological sciences · 2024Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented, but the mechanism underlying this process is poorly understood. Here, we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis, and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. We found that transcription factor MEF2 regulates basal Mfn2 expression in neurons and that excitotoxicity-dependent degradation of MEF2 causes Mfn2 downregulation. Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke.
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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.