The DOI matches its Crossref record; 75 of the 75 references it cites were found in a registry or an index.
Tau Promotes Neurodegeneration via DRP1 Mislocalization In Vivo
Open accessAbstract
Mitochondrial abnormalities have been documented in Alzheimer's disease and related neurodegenerative disorders, but the causal relationship between mitochondrial changes and neurodegeneration, and the specific mechanisms promoting mitochondrial dysfunction, are unclear. Here, we find that expression of human tau results in elongation of mitochondria in both Drosophila and mouse neurons. Elongation is accompanied by mitochondrial dysfunction and cell cycle-mediated cell death, which can be rescued in vivo by genetically restoring the proper balance of mitochondrial fission and fusion. We have previously demonstrated that stabilization of actin by tau is critical for neurotoxicity of the protein. Here, we demonstrate a conserved role for actin and myosin in regulating mitochondrial fission and show that excess actin stabilization inhibits association of the fission protein DRP1 with mitochondria, leading to mitochondrial elongation and subsequent neurotoxicity. Our results thus identify actin-mediated disruption of mitochondrial dynamics as a direct mechanism of tau toxicity in neurons in vivo.
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“Pathologic tau causes an increase in actin stabilization18 that inhibits association of the fission protein Drp1 with mitochondria, leading to mitochondrial elongation and the production of reactive oxygen species44.”
From Tau promotes neurodegeneration through global chromatin relaxation (2014) · cites this paper as [44]
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“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 7,16,44.”
From Tau promotes neurodegeneration through global chromatin relaxation (2014) · cites this paper as [44]
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Targeted gene expression as a means of altering cell fates and generating dominant phenotypes
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Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
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Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
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Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
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Dynamin-related Protein Drp1 Is Required for Mitochondrial Division in Mammalian Cells
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Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357
Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
Xu, X., Pang, Y., & Fan, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02253-4 · Cited by 1,016
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836
An Actin-Dependent Step in Mitochondrial Fission Mediated by the ER-Associated Formin INF2
Korobova, F., Ramabhadran, V., & Higgs, H. N. (2013) · Science · doi:10.1126/science.1228360 · Cited by 817
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718
Metadata
- Authors
- DuBoff, B., Götz, J., & Feany, M. B.
- Affiliations
- Brigham and Women's Hospital (US)
- The University of Queensland (AU)
- ORCID
- Götz, Jürgen
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 75
- Issue
- 4
- Pages
- 618-632
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3428596
- OpenAlex
- W2082970812
- Cited by
- 377
- References
- 75
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 24 · 2023: 30 · 2022: 24 · 2021: 43 · 2020: 26 · 2019: 25 · 2018: 28 · 2017: 30 · 2016: 24 · 2015: 24 · 2014: 29 · 2013: 27 · 2012: 3
- FWCI
- 17.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (F31AG032839, R21AG028074, R01AG033518, R01AG019790)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- tau protein, neurodegeneration, Drp1, mitochondrial fission, mitochondrial fusion, mitochondrial dynamics, mitochondrial elongation, actin filament stabilization, myosin, Alzheimer's disease, mitochondrial dysfunction, tau toxicity, Drosophila neurons, mouse neurons
- MeSH terms
- Actins, Analysis of Variance, Animals, Cytoplasm, Cytoskeletal Proteins, Disease Models, Animal, Drosophila, Gene Expression Regulation, Humans, Microtubule-Associated Proteins, Mitochondria, Mutation, Myosins, Nerve Degeneration, Neurons, tau Proteins, Cell Death, Gelsolin, Cell Cycle Proteins, GTP-Binding Proteins, In Situ Nick-End Labeling, GTP Phosphohydrolases, Mitochondrial Proteins, Tauopathies, ATP Synthetase Complexes, Drosophila Proteins, Animals, Genetically Modified, Dynamins, RNA Interference, MicroRNAs, Green Fluorescent Proteins, Voltage-Dependent Anion Channels, Mice
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