| Title |
PINK1 deficiency sustains cell proliferation by reprogramming glucose metabolism through HIF1
|
|---|---|
| Published in |
Nature Communications, July 2014
|
| DOI | 10.1038/ncomms5514 |
| Pubmed ID | |
| Authors |
Raquel Requejo-Aguilar, Irene Lopez-Fabuel, Emilio Fernandez, Luis M. Martins, Angeles Almeida, Juan P. Bolaños |
| Abstract |
PTEN-induced kinase-1 (PINK1) is a Ser/Thr kinase implicated in familial early-onset Parkinson's disease, and was first reported as a growth suppressor. PINK1 loss-of-function compromises both mitochondrial autophagy and oxidative phosphorylation. Here we report that PINK1 deficiency triggers hypoxia-inducible factor-1α (HIF1α) stabilization in cultured Pink1(-/-) mouse embryonic fibroblasts and primary cortical neurons as well as in vivo. This effect, mediated by mitochondrial reactive oxygen species, led to the upregulation of the HIF1 target, pyruvate dehydrogenase kinase-1, which inhibits PDH activity. Furthermore, we show that HIF1α stimulates glycolysis in the absence of Pink1, and that the promotion of intracellular glucose metabolism by HIF1α stabilization is required for cell proliferation in Pink1(-/-) mice. We propose that loss of Pink1 reprograms glucose metabolism through HIF1α, sustaining increased cell proliferation. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 100 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 1% |
| Australia | 1 | 1% |
| Canada | 1 | 1% |
| Austria | 1 | 1% |
| Unknown | 96 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 20 | 20% |
| Student > Ph. D. Student | 19 | 19% |
| Student > Master | 14 | 14% |
| Student > Bachelor | 10 | 10% |
| Professor > Associate Professor | 4 | 4% |
| Other | 12 | 12% |
| Unknown | 21 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 23 | 23% |
| Biochemistry, Genetics and Molecular Biology | 22 | 22% |
| Neuroscience | 16 | 16% |
| Medicine and Dentistry | 7 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 5% |
| Other | 5 | 5% |
| Unknown | 22 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 20. 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 07 April 2023.
All research outputs
#1,880,410
of 25,654,566 outputs
Outputs from Nature Communications
#25,274
of 57,974 outputs
Outputs of similar age
#18,275
of 240,559 outputs
Outputs of similar age from Nature Communications
#262
of 655 outputs
Altmetric has tracked 25,654,566 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 57,974 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 55.4. This one has gotten more attention than average, scoring higher than 56% 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 240,559 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 92% of its contemporaries.
We're also able to compare this research output to 655 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.