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dATF4 regulation of mitochondrial folate-mediated one-carbon metabolism is neuroprotective

Overview of attention for article published in Cell Death & Differentiation, February 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#2 of 1,087)
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
9 news outlets
blogs
1 blog
twitter
13 tweeters
facebook
9 Facebook pages
video
1 video uploader

Readers on

mendeley
6 Mendeley
Title
dATF4 regulation of mitochondrial folate-mediated one-carbon metabolism is neuroprotective
Published in
Cell Death & Differentiation, February 2017
DOI 10.1038/cdd.2016.158
Pubmed ID
Authors

Celardo, Ivana, Lehmann, Susann, Costa, Ana C, Loh, Samantha HY, Miguel Martins, L, Ivana Celardo, Susann Lehmann, Ana C Costa, Samantha HY Loh, L Miguel Martins, Costa, Ana C., Loh, Samantha H. Y., Martins, L. Miguel

Abstract

Neurons rely on mitochondria as their preferred source of energy. Mutations in PINK1 and PARKIN cause neuronal death in early-onset Parkinson's disease (PD), thought to be due to mitochondrial dysfunction. In Drosophila pink1 and parkin mutants, mitochondrial defects lead to the compensatory upregulation of the mitochondrial one-carbon cycle metabolism genes by an unknown mechanism. Here we uncover that this branch is triggered by the activating transcription factor 4 (ATF4). We show that ATF4 regulates the expression of one-carbon metabolism genes SHMT2 and NMDMC as a protective response to mitochondrial toxicity. Suppressing Shmt2 or Nmdmc caused motor impairment and mitochondrial defects in flies. Epistatic analyses showed that suppressing the upregulation of Shmt2 or Nmdmc deteriorates the phenotype of pink1 or parkin mutants. Conversely, the genetic enhancement of these one-carbon metabolism genes in pink1 or parkin mutants was neuroprotective. We conclude that mitochondrial dysfunction caused by mutations in the Pink1/Parkin pathway engages ATF4-dependent activation of one-carbon metabolism as a protective response. Our findings show a central contribution of ATF4 signalling to PD that may represent a new therapeutic strategy. A video abstract for this article is available at https://youtu.be/cFJJm2YZKKM.Cell Death and Differentiation advance online publication, 17 February 2017; doi:10.1038/cdd.2016.158.

Twitter Demographics

The data shown below were collected from the profiles of 13 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 33%
Researcher 2 33%
Student > Postgraduate 1 17%
Other 1 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 67%
Biochemistry, Genetics and Molecular Biology 2 33%

Attention Score in Context

This research output has an Altmetric Attention Score of 91. 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 13 June 2017.
All research outputs
#85,034
of 7,917,378 outputs
Outputs from Cell Death & Differentiation
#2
of 1,087 outputs
Outputs of similar age
#6,673
of 229,884 outputs
Outputs of similar age from Cell Death & Differentiation
#1
of 44 outputs
Altmetric has tracked 7,917,378 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,087 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one has done particularly well, scoring higher than 99% 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 229,884 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.