• Login
    View Item 
    •   Home
    • Research
    • Articles
    • View Item
    •   Home
    • Research
    • Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of KAUSTCommunitiesIssue DateSubmit DateThis CollectionIssue DateSubmit Date

    My Account

    Login

    Quick Links

    Open Access PolicyORCID LibguidePlumX LibguideSubmit an Item

    Statistics

    Display statistics

    Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Type
    Article
    Authors
    Lambert, Hélène Perreten
    Zenger, Manuel
    Azarias, Guillaume
    Chatton, Jean Yves
    Magistretti, Pierre J. cc
    Lengacher, Sylvain
    KAUST Department
    Bioscience Program
    Biological and Environmental Sciences and Engineering (BESE) Division
    Date
    2014-09-18
    Online Publication Date
    2014-09-18
    Print Publication Date
    2014-11-07
    Permanent link to this record
    http://hdl.handle.net/10754/563762
    
    Metadata
    Show full item record
    Abstract
    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.
    Citation
    Perreten Lambert, H., Zenger, M., Azarias, G., Chatton, J.-Y., Magistretti, P. J., & Lengacher, S. (2014). Control of Mitochondrial pH by Uncoupling Protein 4 in Astrocytes Promotes Neuronal Survival. Journal of Biological Chemistry, 289(45), 31014–31028. doi:10.1074/jbc.m114.570879
    Sponsors
    This work was supported by Swiss National Science Foundation Grants 108336 (to P. J. M.) and 31003A-135720 (to J. Y. C.).
    Publisher
    American Society for Biochemistry & Molecular Biology (ASBMB)
    Journal
    Journal of Biological Chemistry
    DOI
    10.1074/jbc.M114.570879
    PubMed ID
    25237189
    PubMed Central ID
    PMC4223307
    Additional Links
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223307
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M114.570879
    Scopus Count
    Collections
    Articles; Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program

    entitlement

    Related articles

    • Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress.
    • Authors: Liu D, Chan SL, de Souza-Pinto NC, Slevin JR, Wersto RP, Zhan M, Mustafa K, de Cabo R, Mattson MP
    • Issue date: 2006
    • Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity.
    • Authors: Kwok KH, Ho PW, Chu AC, Ho JW, Liu HF, Yiu DC, Chan KH, Kung MH, Ramsden DB, Ho SL
    • Issue date: 2010 Sep 15
    • Mitochondrial UCP4 attenuates MPP+ - and dopamine-induced oxidative stress, mitochondrial depolarization, and ATP deficiency in neurons and is interlinked with UCP2 expression.
    • Authors: Chu AC, Ho PW, Kwok KH, Ho JW, Chan KH, Liu HF, Kung MH, Ramsden DB, Ho SL
    • Issue date: 2009 Mar 15
    • Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells.
    • Authors: Chan SL, Liu D, Kyriazis GA, Bagsiyao P, Ouyang X, Mattson MP
    • Issue date: 2006 Dec 8
    • Toward understanding the mechanism of ion transport activity of neuronal uncoupling proteins UCP2, UCP4, and UCP5.
    • Authors: Hoang T, Smith MD, Jelokhani-Niaraki M
    • Issue date: 2012 May 15
    DSpace software copyright © 2002-2021  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service hosted by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items. For anonymous users the allowed maximum amount is 50 search results.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.