ArticleNeuromolecular medicine2006
Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.
Article in Neuromolecular medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 182 citations in OpenAlex.
- Molecular mechanisms of mitochondrial uncoupling: focus on 2,4-dinitrophenol.European biophysics journal : EBJ · 2026Review
- Astrocyte Mitochondrial UCP4 Reprograms Neuronal Network Oscillations via GDNF-Dependent KCells · 2026Article
- Unraveling the metabolic gene expression and energetic patterns of the seasonally acclimatized gilthead seabream.Fish physiology and biochemistry · 2025Article
- Challenges and opportunities in inflammatory bowel disease: from current therapeutic strategies to organoid-based models.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Exploring the role of mitochondrial uncoupling protein 4 in brain metabolism: implications for Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Mechanisms underlying retardation of aging by dietary energy restriction.Pathology international · 2023Review
- Lipid Adaptations against Oxidative Challenge in the Healthy Adult Human Brain.Antioxidants (Basel, Switzerland) · 2023Review
- Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Protective Effect of Flavonoids against Methylglyoxal-Induced Oxidative Stress in PC-12 Neuroblastoma Cells and Its Structure-Activity Relationships.Molecules (Basel, Switzerland) · 2022Article
- The Cholinergic Pathway and MitoKStroke (Hoboken, N.J.) · 2022Article
- Eicosatetraynoic Acid and Butyrate Regulate Human Intestinal Organoid Mitochondrial and Extracellular Matrix Pathways Implicated in Crohn's Disease Strictures.Inflammatory bowel diseases · 2022Article
- Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment.Cell death & disease · 2022Article
- A novel 8-gene panel for prediction of early biochemical recurrence in patients with prostate cancer after radical prostatectomy.American journal of cancer research · 2022Article
- Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Dual imaging of dendritic spines and mitochondriaNeurobiology of stress · 2021Article
- Mitochondrial Uncoupling Proteins (UCPs) as Key Modulators of ROS Homeostasis: A Crosstalk between Diabesity and Male Infertility?Antioxidants (Basel, Switzerland) · 2021Review
- Benefit of a single simulated hypobaric hypoxia in healthy mice performance and analysis of mitochondria-related gene changes.Scientific reports · 2021Article
- Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium.Frontiers in pharmacology · 2021Article
- Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential (Deltapsim) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements. Neural cells with increased levels of UCP4 exhibit decreased Deltapsim, reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of Deltapsim to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochondrial respiration to glycolysis, thereby maintaining cellular ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload.
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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.