Evidence map›Paper›PMID 39772672›Full record

ArticleScience advances2025

NAC regulates metabolism and cell fate in intestinal stem cells.

Sofia Ramalho, Ferhat Alkan, Stefan Prekovic, Katarzyna Jastrzebski, Eric Pintó Barberà, Liesbeth Hoekman, Maarten Altelaar, Cecilia de Heus, Nalan Liv, Maria J Rodríguez-Colman and 7 more

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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.

Sofia RamalhoDivision of Oncogenomics, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0002-9091-2657
Ferhat AlkanDivision of Oncogenomics, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0001-6709-9605
Stefan PrekovicCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0002-7051-9321
Katarzyna JastrzebskiDivision of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0002-3062-9016
Eric Pintó BarberàDivision of Oncogenomics, Netherlands Cancer Institute, Amsterdam, Netherlands.
Liesbeth HoekmanProteomics Facility, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0002-3552-6390
Maarten AltelaarBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.ORCID 0000-0001-5093-5945
Cecilia de HeusCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Nalan LivCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0003-2654-9117
Maria J Rodríguez-ColmanCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Mehmet YilmazCenter for Molecular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Rob van der KammenDivision of Oncogenomics, Netherlands Cancer Institute, Amsterdam, Netherlands.
Juliette FedryMRC Laboratory of Molecular Biology, Cambridge, UK.ORCID 0000-0002-6592-4269
Mark C de GooijerDivision of Pharmacology, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0002-2812-991X
Saskia Jacoba Elisabeth SuijkerbuijkDivision of Developmental Biology, Institute of Biodynamics and Biocomplexity, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.ORCID 0000-0002-3197-1307
William J FallerDivision of Oncogenomics, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0002-0738-2254
Joana SilvaDivision of Oncogenomics, Netherlands Cancer Institute, Amsterdam, Netherlands.ORCID 0000-0001-5301-1799

Funding

Medical Research Council MC_UP_1201/32
6 · The paper itself

Abstract

Intestinal stem cells (ISCs) face the challenge of integrating metabolic demands with unique regenerative functions. Studies have shown an intricate interplay between metabolism and stem cell capacity; however, it is still not understood how this process is regulated. Combining ribosome profiling and CRISPR screening in intestinal organoids, we identify the nascent polypeptide-associated complex (NAC) as a key mediator of this process. Our findings suggest that NAC is responsible for relocalizing ribosomes to the mitochondria and regulating ISC metabolism. Upon NAC inhibition, intestinal cells show decreased import of mitochondrial proteins, which are needed for oxidative phosphorylation, and, consequently, enable the cell to maintain a stem cell identity. Furthermore, we show that overexpression of NACα is sufficient to drive mitochondrial respiration and promote ISC identity. Ultimately, our results reveal the pivotal role of NAC in regulating ribosome localization, mitochondrial metabolism, and ISC function, providing insights into the potential mechanism behind it.

Indexed as

IntestinesMitochondriaRibosomesStem CellsAnimalsCell DifferentiationIntestinal MucosaMiceMitochondrial ProteinsOrganoidsOxidative PhosphorylationMitochondrial Proteins

Identifiers

PMID39772672
PMCPMC11708876

What Socratic 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 Socratic graph.