Evidence map›Paper›PMID 38467609›Full record

ArticleCell death & disease2024

Genome-wide CRISPR/Cas9 screen shows that loss of GET4 increases mitochondria-endoplasmic reticulum contact sites and is neuroprotective.

Emma L Wilson, Yizhou Yu, Nuno S Leal, James A Woodward, Nikolaos Patikas, Jordan L Morris, Sarah F Field, William Plumbly, Vincent Paupe, Suvagata R Chowdhury and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Endoplasmic reticulum-Mitochondria Coupling in Alzheimer's Disease.Contact (Thousand Oaks (Ventura County, Calif.))
    Review
  10. Approaches to Organelle Spacing at Membrane Contact Sites.Contact (Thousand Oaks (Ventura County, Calif.))
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Emma L WilsonUK Dementia Research Institute, University of Cambridge, Clifford Albutt building, Cambridge biomedical campus, Cambridge, CB2 0AH, UK.ORCID 0000-0002-5600-1622
Yizhou YuMRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.ORCID 0000-0002-4800-9392
Nuno S LealMRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.
James A WoodwardMRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.
Nikolaos PatikasUK Dementia Research Institute, University of Cambridge, Clifford Albutt building, Cambridge biomedical campus, Cambridge, CB2 0AH, UK.ORCID 0000-0002-3978-0134
Jordan L MorrisMRC Mitochondrial Biology Unit, University of Cambridge, The Keith Peters building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Sarah F FieldUK Dementia Research Institute, University of Cambridge, Clifford Albutt building, Cambridge biomedical campus, Cambridge, CB2 0AH, UK.
William PlumblyUK Dementia Research Institute, University of Cambridge, Clifford Albutt building, Cambridge biomedical campus, Cambridge, CB2 0AH, UK.
Vincent PaupeMRC Mitochondrial Biology Unit, University of Cambridge, The Keith Peters building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Suvagata R ChowdhuryMRC Mitochondrial Biology Unit, University of Cambridge, The Keith Peters building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
Robin AntrobusCambridge Institute for Medical Research, University of Cambridge, The Keith Peters Building, Cambridge Biomedical Campus, Hills Rd, Cambridge, CB2 0XY, UK.
Georgina E LindopCambridge Advanced Imaging Centre, University of Cambridge, Anatomy Building, Downing Site, Cambridge, CB2 3DY, UK.ORCID 0009-0000-8664-6985
Yusuf M AdiaMRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.ORCID 0009-0001-6538-0919
Samantha H Y LohMRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK.
Julien PrudentMRC Mitochondrial Biology Unit, University of Cambridge, The Keith Peters building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK. julien.prudent@mrc-mbu.cam.ac.uk.ORCID 0000-0003-3821-6088
L Miguel MartinsMRC Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QR, UK. martins.lmiguel@gmail.com.ORCID 0000-0002-3019-4809
Emmanouil MetzakopianUK Dementia Research Institute, University of Cambridge, Clifford Albutt building, Cambridge biomedical campus, Cambridge, CB2 0AH, UK. mano982@gmail.com.ORCID 0000-0003-2893-9741
University of Cambridge · GBBabraham Bioscience Technologies (United Kingdom) · GBBridge University · SSMRC Mitochondrial Biology Unit · GB

Funding

Medical Research Council MC_UU_00028/5
6 · The paper itself

Abstract

Organelles form membrane contact sites between each other, allowing for the transfer of molecules and signals. Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) are cellular subdomains characterized by close apposition of mitochondria and ER membranes. They have been implicated in many diseases, including neurodegenerative, metabolic, and cardiac diseases. Although MERCS have been extensively studied, much remains to be explored. To uncover novel regulators of MERCS, we conducted a genome-wide, flow cytometry-based screen using an engineered MERCS reporter cell line. We found 410 genes whose downregulation promotes MERCS and 230 genes whose downregulation decreases MERCS. From these, 29 genes were selected from each population for arrayed screening and 25 were validated from the high population and 13 from the low population. GET4 and BAG6 were highlighted as the top 2 genes that upon suppression increased MERCS from both the pooled and arrayed screens, and these were subjected to further investigation. Multiple microscopy analyses confirmed that loss of GET4 or BAG6 increased MERCS. GET4 and BAG6 were also observed to interact with the known MERCS proteins, inositol 1,4,5-trisphosphate receptors (IP3R) and glucose-regulated protein 75 (GRP75). In addition, we found that loss of GET4 increased mitochondrial calcium uptake upon ER-Ca

Indexed as

CRISPR-Cas SystemsMitochondria Associated MembranesCalciumEndoplasmic ReticulumMitochondriaMitochondrial MembranesCalcium

Identifiers

PMID38467609
PMCPMC10928201
OpenAlexW4392662832

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.