ArticleScience advances2020
Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 105 citations in OpenAlex.
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- Norepinephrine regulates hippocampal mitochondrial biogenesis via β2-adrenergic receptor signaling and PGC-1α.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Reviving mitochondria to restore the mind: stem cell-based bioenergetic rescue in Parkinson's disease.Neurodegenerative disease management · 2026Review
- Evaluating Variability in Extracellular Vesicle Characterization Across Measurement Techniques.Journal of extracellular biology · 2026Article
- 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
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- Reversibility and therapeutic feasibility of DNM1L-associated neurodevelopmental disorders.Experimental & molecular medicine · 2026Article
- Mitochondrial Metabolic Reprogramming of Cortical Neurons by Prenatal Exposure to Corticosterone: A Shift from ATP Synthesis to Membrane Potential Maintenance.Experimental neurobiology · 2026Article
- Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells.Frontiers in cell and developmental biology · 2026Article
- Roles of Oxidative Phosphorylation and Fatty Acid Oxidation in Neuroinflammation Induced by Lipopolysaccharide in Hypothalamic Neuronal Cells.International journal of inflammation · 2026Article
- Metformin Restores Mitochondrial Function and Neurogenesis in POLG Patient-Derived Brain Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Neuro-Melanoma Singularity: Convergent Evolution of Neural and Melanocytic Networks in Brain Metastatic Adaptation.Biomolecules · 2025Review
- Understanding metabolic resilience by unraveling temporal dynamics of cellular responses.Trends in endocrinology and metabolism: TEM · 2025Review
- CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology.Science advances · 2025Article
- Imaging Cellular Metabolic Rewiring with SuMMIT-SRS.bioRxiv : the preprint server for biology · 2025Article
- Article
- CRISPR and Artificial Intelligence in Neuroregeneration: Closed-Loop Strategies for Precision Medicine, Spinal Cord Repair, and Adaptive Neuro-Oncology.International journal of molecular sciences · 2025Review
- Charcot-Marie-Tooth type 2A variants of mitofusin 2 sensitize cells to apoptotic cell death.Journal of cell science · 2025Article
- Mitochondria-centred metabolomic map of inclusion body myositis: sex-specific alterations in central carbon metabolism.Annals of the rheumatic diseases · 2025Article
- Mechanism and application of thiol-disulfide redox biosensors with a fluorescence-lifetime readout.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurodegeneration in mitochondrial disorders is considered irreversible because of limited metabolic plasticity in neurons, yet the cell-autonomous implications of mitochondrial dysfunction for neuronal metabolism in vivo are poorly understood. Here, we profiled the cell-specific proteome of Purkinje neurons undergoing progressive OXPHOS deficiency caused by disrupted mitochondrial fusion dynamics. We found that mitochondrial dysfunction triggers a profound rewiring of the proteomic landscape, culminating in the sequential activation of precise metabolic programs preceding cell death. Unexpectedly, we identified a marked induction of pyruvate carboxylase (PCx) and other anaplerotic enzymes involved in replenishing tricarboxylic acid cycle intermediates. Suppression of PCx aggravated oxidative stress and neurodegeneration, showing that anaplerosis is protective in OXPHOS-deficient neurons. Restoration of mitochondrial fusion in end-stage degenerating neurons fully reversed these metabolic hallmarks, thereby preventing cell death. Our findings identify a previously unappreciated pathway conferring resilience to mitochondrial dysfunction and show that neurodegeneration can be reversed even at advanced disease stages.
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Registered trials
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.