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    Mitochondrial DNA Manipulations Affect Tau Oligomerization

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    Weidling_2020.pdf (1.384Mb)
    Issue Date
    2020-06-02
    Author
    Weidling, Ian W.
    Wilkins, Heather M.
    Koppel, Scott J.
    Hutfles, Lewis
    Wang, Xiaowan
    Kalani, Anuradha
    Menta, Blaise W.
    Ryan, Benjamin
    Perez-Ortiz, Judit
    Gamblin, Chris
    Swerdlow, Russell H.
    Publisher
    IOS Press
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright 2020 The Author(s).
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    Abstract
    Background:Mitochondrial dysfunction and tau aggregation occur in Alzheimer’s disease (AD), and exposing cells or rodents to mitochondrial toxins alters their tau. Objective:To further explore how mitochondria influence tau, we measured tau oligomer levels in human neuronal SH-SY5Y cells with different mitochondrial DNA (mtDNA) manipulations. Methods:Specifically, we analyzed cells undergoing ethidium bromide-induced acute mtDNA depletion, ρ0 cells with chronic mtDNA depletion, and cytoplasmic hybrid (cybrid) cell lines containing mtDNA from AD subjects. Results:We found cytochrome oxidase activity was particularly sensitive to acute mtDNA depletion, evidence of metabolic re-programming in the ρ0 cells, and a relatively reduced mtDNA content in cybrids generated through AD subject mitochondrial transfer. In each case tau oligomer levels increased, and acutely depleted and AD cybrid cells also showed a monomer to oligomer shift. Conclusion:We conclude a cell’s mtDNA affects tau oligomerization. Overlapping tau changes across three mtDNA-manipulated models establishes the reproducibility of the phenomenon, and its presence in AD cybrids supports its AD-relevance.
    URI
    http://hdl.handle.net/1808/32459
    DOI
    https://doi.org/10.3233/JAD-200286
    Collections
    • Molecular Biosciences Scholarly Works [590]
    Citation
    Weidling, I. W., Wilkins, H. M., Koppel, S. J., Hutfles, L., Wang, X., Kalani, A., Menta, B. W., Ryan, B., Perez-Ortiz, J., Gamblin, T. C., & Swerdlow, R. H. (2020). Mitochondrial DNA Manipulations Affect Tau Oligomerization. Journal of Alzheimer's disease : JAD, 77(1), 149–163. https://doi.org/10.3233/JAD-200286

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    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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