Cited by 267Alzheimer's disease research and treatmentsAutophagy in Disease and TherapyParkinson's Disease Mechanisms and Treatments

Disease-associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria

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Cummins, Nadia, Tweedie, Andrea, Zuryn, Steven, Bertran‐Gonzalez, Jesus, Götz, Jürgen·2019·The EMBO Journal

Abstract

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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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
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
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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