Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria
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nervous system, hTau expression reduced mitophagy, whereas hP301L expression completely inhibited it. These effects were not due to changes in the mitochondrial membrane potential or the cytoskeleton, as tau specifically impaired Parkin recruitment to defective mitochondria by sequestering it in the cytosol. This sequestration was mediated by aberrant interactions of Parkin with the projection domain of tau. As mitochondria are dysfunctional in neurodegenerative conditions, these data suggest a vicious cycle, with tau also inhibiting the degradation of damaged mitochondria.
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Recent studies suggest that there is an accumulation of damaged mitochondria in Alzheimer's disease caused by defective mitophagy.
“Additionally, recent studies suggest that there is an accumulation of damaged mitochondria in AD caused by defective mitophagy (Cummins et al., 2019; Fang et al., 2019).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Cummins et al., 2019
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Self-citation
- Authors
- Cummins, N., Tweedie, A., Zuryn, S., Bertran‐Gonzalez, J., & Götz, J.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Götz, Jürgen
- Venue
- The EMBO Journal
- Published
- 2018-12-11
- Volume
- 38
- Issue
- 3
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC6356067
- OpenAlex
- W2903973081
- Cited by
- 267
- References
- 68
- Citations by year
- 2026: 30 · 2025: 34 · 2024: 31 · 2023: 29 · 2022: 44 · 2021: 46 · 2020: 35 · 2019: 18
- FWCI
- 17.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Department of Education and Training | Australian Research Council (30100078, DP130101932, LE130100078)
- Department of Health | National Health and Medical Research Council (GNT1037746, GNT1003150, GNT1127999, GNT1128381, APP1128381)
- Federal Government of Australia (ACT900116)
- State Government of Queensland
- Stafford Fox Senior Research Fellowship
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- tau protein, mitophagy, Parkin, P301L tau, mitochondrial dysfunction, neurodegeneration, projection domain, mitochondrial quality control
- MeSH terms
- Animals, Male, Mice, Transgenic, Mitochondria, Neuroblastoma, Neurons, Tumor Cells, Cultured, tau Proteins, Caenorhabditis elegans, Protein Transport, Ubiquitin-Protein Ligases, Mice, Membrane Potential, Mitochondrial, Mitophagy
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