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Mitochondrial DNA Manipulations Affect Tau Oligomerization
dc.contributor.author | Weidling, Ian W. | |
dc.contributor.author | Wilkins, Heather M. | |
dc.contributor.author | Koppel, Scott J. | |
dc.contributor.author | Hutfles, Lewis | |
dc.contributor.author | Wang, Xiaowan | |
dc.contributor.author | Kalani, Anuradha | |
dc.contributor.author | Menta, Blaise W. | |
dc.contributor.author | Ryan, Benjamin | |
dc.contributor.author | Perez-Ortiz, Judit | |
dc.contributor.author | Gamblin, Chris | |
dc.contributor.author | Swerdlow, Russell H. | |
dc.date.accessioned | 2022-01-20T16:24:49Z | |
dc.date.available | 2022-01-20T16:24:49Z | |
dc.date.issued | 2020-06-02 | |
dc.identifier.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 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32459 | |
dc.description.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. | en_US |
dc.publisher | IOS Press | en_US |
dc.rights | Copyright 2020 The Author(s). | en_US |
dc.subject | Alzheimer’s disease | en_US |
dc.subject | Mitochondria | en_US |
dc.subject | Mitochondrial DNA | en_US |
dc.subject | Oligomers | en_US |
dc.subject | Tau | en_US |
dc.title | Mitochondrial DNA Manipulations Affect Tau Oligomerization | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Gamblin, T. Chris | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.3233/JAD-200286 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7962146 | en_US |
dc.rights.accessrights | openAccess | en_US |