Tau promotes neurodegeneration via DRP1 mislocalization in vivo

DuBoff, Brian, Goetz, Juergen and Feany, Mel B. (2012) Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron, 75 4: 618-632. doi:10.1016/j.neuron.2012.06.026

Author DuBoff, Brian
Goetz, Juergen
Feany, Mel B.
Title Tau promotes neurodegeneration via DRP1 mislocalization in vivo
Journal name Neuron   Check publisher's open access policy
ISSN 0896-6273
Publication date 2012-08-23
Sub-type Article (original research)
DOI 10.1016/j.neuron.2012.06.026
Volume 75
Issue 4
Start page 618
End page 632
Total pages 15
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
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.
Keyword Dynamin-related protein
Alzheimers-Disease brain
Dominant optic atrophy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
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Citation counts: TR Web of Science Citation Count  Cited 110 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 113 times in Scopus Article | Citations
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Created: Wed, 07 Nov 2012, 00:58:38 EST by Debra McMurtrie on behalf of Queensland Brain Institute