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Mutant TDP-43 does not impair mitochondrial bioenergetics in vitro and in vivo

Overview of attention for article published in Molecular Neurodegeneration, May 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • Average Attention Score compared to outputs of the same age and source

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1 news outlet
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1 tweeter

Citations

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17 Dimensions

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36 Mendeley
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Title
Mutant TDP-43 does not impair mitochondrial bioenergetics in vitro and in vivo
Published in
Molecular Neurodegeneration, May 2017
DOI 10.1186/s13024-017-0180-1
Pubmed ID
Authors

Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi

Abstract

Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant protein. Here, we investigated the presence of bioenergetic defects in the brain of transgenic mice expressing human mutant TDP-43 (TDP-43(A315T) mice), patient derived fibroblasts, and human cells expressing mutant forms of TDP-43. In the brain of TDP-43(A315T) mice, TDP-43 mutant fibroblasts, and cells expressing mutant TDP-43, we tested several bioenergetics parameters, including mitochondrial respiration, ATP synthesis, and calcium handling. Differences between mutant and control samples were evaluated by student t-test or by ANOVA, followed by Bonferroni correction, when more than two groups were compared. Mitochondrial localization of TDP-43 was investigated by immunocytochemistry in fibroblasts and by subcellular fractionation and western blot of mitochondrial fractions in mouse brain. We did not observe defects in any of the mitochondrial bioenergetic functions that were tested in TDP-43 mutants. We detected a small amount of TDP-43(A315T) peripherally associated with brain mitochondria. However, there was no correlation between TDP-43 associated with mitochondria and respiratory chain dysfunction. In addition, we observed increased calcium uptake in mitochondria from TDP-43(A315T) mouse brain and cells expressing A315T mutant TDP-43. While alterations of mitochondrial morphology and dynamics in TDP-43 mutant neurons are well established, the present study did not demonstrate oxidative phosphorylation defects in TDP-43 mutants, in vitro and in vivo. On the other hand, the increase in mitochondrial calcium uptake in A315T TDP-43 mutants was an intriguing finding, which needs to be investigated further to understand its mechanisms and potential pathogenic implications.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Germany 1 3%
Unknown 34 94%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 25%
Student > Bachelor 7 19%
Researcher 4 11%
Student > Master 3 8%
Student > Postgraduate 2 6%
Other 5 14%
Unknown 6 17%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 36%
Agricultural and Biological Sciences 7 19%
Neuroscience 5 14%
Medicine and Dentistry 2 6%
Social Sciences 1 3%
Other 3 8%
Unknown 5 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 May 2017.
All research outputs
#1,124,031
of 9,896,588 outputs
Outputs from Molecular Neurodegeneration
#144
of 484 outputs
Outputs of similar age
#45,995
of 263,504 outputs
Outputs of similar age from Molecular Neurodegeneration
#13
of 22 outputs
Altmetric has tracked 9,896,588 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 484 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 263,504 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.