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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation
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|---|---|
| Published in |
Molecular Neurodegeneration, March 2023
|
| DOI | 10.1186/s13024-023-00602-x |
| Pubmed ID | |
| Authors |
Vyara Todorova, Mia Fee Stauffacher, Luca Ravotto, Sarah Nötzli, Duygu Karademir, Lynn J. A. Ebner, Cornelia Imsand, Luca Merolla, Stefanie M. Hauck, Marijana Samardzija, Aiman S. Saab, L. Felipe Barros, Bruno Weber, Christian Grimm |
| Abstract |
Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR. We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation. PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration. Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 14 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 3 | 21% |
| Unspecified | 2 | 14% |
| Student > Postgraduate | 1 | 7% |
| Student > Bachelor | 1 | 7% |
| Student > Doctoral Student | 1 | 7% |
| Other | 2 | 14% |
| Unknown | 4 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 3 | 21% |
| Agricultural and Biological Sciences | 3 | 21% |
| Unspecified | 2 | 14% |
| Materials Science | 1 | 7% |
| Chemistry | 1 | 7% |
| Other | 0 | 0% |
| Unknown | 4 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 08 March 2023.
All research outputs
#13,610,027
of 23,956,119 outputs
Outputs from Molecular Neurodegeneration
#682
of 886 outputs
Outputs of similar age
#159,312
of 422,678 outputs
Outputs of similar age from Molecular Neurodegeneration
#21
of 22 outputs
Altmetric has tracked 23,956,119 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 886 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.4. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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 422,678 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 61% 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 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.