ArticleProceedings of the National Academy of Sciences of the United States of America2010
Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed, 297 citations in OpenAlex.
- A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Beyond Neurodegeneration: White Matter Vacuolation as a Primary Myelin Defect.International journal of molecular sciences · 2026Review
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026Review
- In Vivo 4D Oxy-Wavelet MRI as a Non-Invasive Biomarker of Brain Mitochondrial Function across the Lifespan.bioRxiv : the preprint server for biology · 2026Article
- Preclinical and first-in-human evidence of 4-hydroxybenzoic acid for mitochondrial COQ2 deficiency.Brain : a journal of neurology · 2026Article
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Pioglitazone Ameliorates Mitochondrial Oxidative Stress and Inflammation via AMPK-Dependent Inhibition of Mitochondrial Fission in Leigh Syndrome.Cell proliferation · 2026Article
- The succinate prodrug NV354 prevents brain lesions and late-stage motor dysfunction in mitochondrial complex I deficiency.iScience · 2026Article
- Cell-intrinsic vulnerability and immune activation cooperate to drive degeneration in a mitochondrial complex I deficiency model of optic neuropathy.Journal of neuroinflammation · 2026Article
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.Investigative ophthalmology & visual science · 2026Article
- A genetically encoded bifunctional enzyme mitigates redox imbalance and lipotoxicity.Nature metabolism · 2026Article
- Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice.EMBO molecular medicine · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Energy Metabolism Under Stress: Late-Stage Leigh Syndrome Reveals Profound Cardiometabolic Perturbations in Ndufs4 KO Mice.Journal of inherited metabolic disease · 2026Article
- Dysfunctional LHX6 pallido-subthalamic projections mediate epileptic events in a mouse model of Leigh syndrome.The Journal of clinical investigation · 2025Article
- Expanding research and care for Leigh syndrome: efforts of a patient-led advocacy organization.Research involvement and engagement · 2025Article
- Article
- Ndufs4GeroScience · 2025Review
108 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
To explore the lethal, ataxic phenotype of complex I deficiency in Ndufs4 knockout (KO) mice, we inactivated Ndufs4 selectively in neurons and glia (NesKO mice). NesKO mice manifested the same symptoms as KO mice including retarded growth, loss of motor ability, breathing abnormalities, and death by approximately 7 wk. Progressive neuronal deterioration and gliosis in specific brain areas corresponded to behavioral changes as the disease advanced, with early involvement of the olfactory bulb, cerebellum, and vestibular nuclei. Neurons, particularly in these brain regions, had aberrant mitochondrial morphology. Activation of caspase 8, but not caspase 9, in affected brain regions implicate the initiation of the extrinsic apoptotic pathway. Limited caspase 3 activation and the predominance of ultrastructural features of necrotic cell death suggest a switch from apoptosis to necrosis in affected neurons. These data suggest that dysfunctional complex I in specific brain regions results in progressive glial activation that promotes neuronal death that ultimately results in mortality.
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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.