The DOI matches its Crossref record; 67 of the 69 references it cites were found in a registry or an index.
Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability
Open accessPublished version of a preprint
Abstract
The selenoprotein glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid peroxides into nontoxic lipid alcohols. GPX4 has emerged as a promising therapeutic target for cancer treatment, but some cancer cells are resistant to ferroptosis triggered by GPX4 inhibition. Using a chemical-genetic screen, we identify LRP8 (also known as ApoER2) as a ferroptosis resistance factor that is upregulated in cancer. Loss of LRP8 decreases cellular selenium levels and the expression of a subset of selenoproteins. Counter to the canonical hierarchical selenoprotein regulatory program, GPX4 levels are strongly reduced due to impaired translation. Mechanistically, low selenium levels result in ribosome stalling at the inefficiently decoded GPX4 selenocysteine UGA codon, leading to ribosome collisions, early translation termination and proteasomal clearance of the N-terminal GPX4 fragment. These findings reveal rewiring of the selenoprotein hierarchy in cancer cells and identify ribosome stalling and collisions during GPX4 translation as ferroptosis vulnerabilities in cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“LRP8 has been recently shown to affect ferroptosis by regulating the level of selenoprotein GPX4 in cancer cells (54–56).”
From Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis (2024) · cites this paper as [54]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
Self-citationFerroptosis: mechanisms, biology and role in disease
Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,973
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695
Self-citationGenome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. S., & Weissman, J. S. (2009) · Science · doi:10.1126/science.1168978 · Cited by 3,853
Self-citationThe CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
Bersuker, K., Hendricks, J. M., Li, Z., Magtanong, L., Ford, B., Tang, P. H., Roberts, M. A., Tong, B., Maimone, T. J., Zoncu, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1705-2 · Cited by 3,703
Self-citation
Cited by
Sorted by citations
Items 101–134 of 134
choros: correction of sequence-based biases for accurate quantification of ribosome profiling dataPreprint
Mok, A., Tunney, R. J., Benegas, G., Wallace, E. W. J., & Lareau, L. F. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.21.529452 · Cited by 3
Uesugi, S., Mori, Y., Hakozaki, M., Kanno, Y., Yano, A., Abe‐Kanoh, N., Kimura, K., Sato, H., & Kobayashi, S. (2025) · Fitoterapia · doi:10.1016/j.fitote.2025.106929 · Cited by 2
Zhang, L., Zhang, L., Zhao, J., Zhang, W. Y., & Zhang, H. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05424-0 · Cited by 3
Aoyama, Y., Yamazaki, H., & Inoue, D. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.105346 · Cited by 3
Wang, F., Huang, H., Zhang, R., Wei, X., Wang, Z., Qiu, X., Gao, Y., Wang, X., Xie, W., Zhang, H., et al. (2026) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-026-03645-2 · Cited by 2
Jiao, J., Song, L., Xu, S., Xue, Y., Liao, Y., Xu, K., Wen, Q., Xiang, K., Chen, R., Dong, X., et al. (2026) · Gut · doi:10.1136/gutjnl-2025-336422 · Cited by 2
Liu, K., Liu, Y., Thorne, R. F., Meng, F., Liu, Y., Wu, M., & Liu, L. (2026) · Molecular Cell · doi:10.1016/j.molcel.2026.04.026 · Cited by 2
Chen, X., Lu, Y., Wang, Y., Kou, Y., Gu, Y., & Lin, Y. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1852342 · Cited by 2
Adapt or Perish: Efficient Selenocysteine Insertion Is Critical for Metastasizing Cancer Cells
Lee, N., & Kim, D. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-4442 · Cited by 2
Parallel CRISPR-Cas9 screens reveal mechanisms of PLIN2 and lipid droplet regulationPreprint
Roberts, M. A., Deol, K. K., Lange, M., Leto, D. E., Mathiowetz, A. J., Stevenson, J., Hashemi, S. H., Morgens, D. W., Easter, E., Heydari, K., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.27.505556 · Cited by 2
Self-citationRehfeld, F., Lundstrom, C., Zhang, H., & Mendell, J. T. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.13.682107 · Cited by 3
Local M1 Macrophage Reprogramming with Gluconic Acid-Coated Selenium Nanoparticles
Liao, Z., Ou, D., Hsu, C., Lu, L.-N., Wen, C.-H., Lu, L., Chiu, C.-L., Yang, P., & Tseng, S. ‐. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s556099 · Cited by 1
Wei, X., Cao, Z., Zhou, H., Zhang, J., Liu, S., Liu, J., Yu, C., & Wei, H. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5c18878 · Cited by 1
Poly-GR promotes ferroptosis-associated vulnerability in C9orf72-ALS
Lin, C., Hsieh, W.-C., & Wang, S. (2026) · Cell & Bioscience · doi:10.1186/s13578-026-01574-3 · Cited by 1
Li, M., Zhu, Y., Kageyama, Y., Furudate, K., Kitano, A., Tan, T., Feng, M., Zhou, J., Wang, T., Taylor, R. J., et al. (2026) · Nature Cell Biology · doi:10.1038/s41556-026-02016-5 · Cited by 1
Mechanisms underlying propagation of ferroptotic cell death
Maremonti, F., Dehdari, A., Leinung, N., Pratt, D. A., & Linkermann, A. (2026) · Nature Cell Biology · doi:10.1038/s41556-026-02053-0 · Cited by 2
Deng, L., Liu, K., Peng, J., & Luo, L. (2026) · Medicinal Research Reviews · doi:10.1002/med.70099 · Cited by 1
Targeted extracellular degradation of LRP8 promotes ferroptosis in cancer cells
Zhao, F., Inague, A., Peters-Clarke, T. M., Chen, Y., Ganjave, S. D., Zhang, Y., Miao, K., Yao, Z., Wu, Y., Seto, M. K. C., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2616933123
Self-citationCommonly used organoid culture media prevent ferroptosisPreprint
Eaton, J. K., Chatterji, P., Sweat, Y. Y., Victorio, R. A., Wawer, M. J., & Viswanathan, V. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.29.591759 · Cited by 1
Organelle-specific Mechanisms of Ferroptosis
Chen, X. (2023) · Springer eBooks · doi:10.1007/978-3-031-39171-2_12
Fundamental aspects of selenium and selenoprotein biochemistry: applied value in oncology
Васильевна, С. И., Владимирович, Х. В., Петроченко, Д. В., Salamatina, A. Y., Иоутси, В. А., Furman, Y., Леонидовна, Л. Н., & Валерьевич, Е. И. (2024) · Siberian Journal of Oncology · doi:10.21294/1814-4861-2024-23-5-157-169
リポタンパク質受容体ApoER2によるがん細胞のフェロトーシス制御
Dong-Ho, K. I. M., SUKEDA, H., & SAEKI, S. (2023) · KAGAKU TO SEIBUTSU · doi:10.1271/kagakutoseibutsu.61.574
Transcriptome-wide analysis of protein synthesis: Ribosome profiling and beyond
Dmitriev, S. E., Luppov, D. V., Kats, L., Anisimova, A. S., & Terenin, I. M. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-19110-7.00015-x
IL4i1-sourced oncometabolites promote neuroblastoma cell survivalPreprint
Guyot, C., de Velde, L.-A. V., Kainacher, L., Ruoff, J., Bici, A., Peterson, N. B., Allen, E. K., Steigenberger, B. A., Yeroslaviz, A., Yang, J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.07.669062
Bornkamm, G. W., Kelly, G. L., & Ross, A. M. (2025) · Current topics in microbiology and immunology · doi:10.1007/82_2025_301 · Cited by 2
Demircan, K., Bengtsson, Y., Chillon, T. S., Vallon‐Christersson, J., Sun, Q., Larsson, C., Malmberg, M., Saal, L. H., Rydén, L., Borg, Å., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24187846
IL4i1 activity generates oncometabolites that rescue neuroblastoma cells from oxidative death
Guyot, C., de Velde, L.-A. V., Kainacher, L., Ruoff, J., Bici, A., Peterson, N. B., Ogger, P. P., Allen, E. K., Steigenberger, B. A., Yeroslaviz, A., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117441
Fueling Death: The Metabolic Control of Ferroptosis
Carrà, G., Scalera, A., Barbieri, I., Menga, A., & Porporato, P. E. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-032-12166-0_16
Emerging tools to investigate the contribution of selenium to ferroptosis and beyond
Fazeli, G., Ahn, I. Y., Pluth, M. D., de Paiva, R. E. F., Lee, N., & Angeli, J. P. F. (2026) · Nature Chemical Biology · doi:10.1038/s41589-026-02278-y
CRISPR screens for the discovery of novel ferroptosis targets: progress and perspectives
Yu, W., Cui, Y., Zhao, Q., & Luo, L. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118410
Zeng, F., Chen, X., Long, K., Yu, B., Cai, Y., Cai, Y., & Liu, C. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1959579
Targeting GPX4 and FSP1 to exploit ferroptotic vulnerability in Ewing sarcoma
Mhindu, M. T., Koppenhafer, S. L., Lyons, M. G., Zimmerman, J. A. O., & Gordon, D. J. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1945631
Proteasome inhibition bidirectionally regulates ferroptosis sensitivity
Murray, M. B., Upadhyay, R., Szylo, K. J., Gautam, A., Goncalves, J., Forcina, G. C., Vinayak, A. A., Brandman, O., & Dixon, S. J. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.09.020
Self-citationGut Microbiota–Ferroptosis Crosstalk and Dietary Intervention Strategies
Kong, Q.-M., Jing, Y.-E., Liu, C., Liu, Y.-Y., Lin, X.-Y., Xiao, S.-C., Yin, Z.-Q., Hao, Y., Wang, J.-S., Ma, Y.-Y., et al. (2026) · Food reviews international (Print) · doi:10.1080/87559129.2026.2748297
Metadata
- Authors
- Li, Z., Ferguson, L., Deol, K. K., Roberts, M. A., Magtanong, L., Hendricks, J. M., Mousa, G. A., Kilinc, S., Schaefer, K., Wells, J. A., Bassik, M. C., Goga, A., Dixon, S. J., Ingolia, N. T., & Olzmann, J. A.
- Affiliations
- University of California, Berkeley (US)
- Stanford University (US)
- University of California, San Francisco (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Corresponding author
- Olzmann, James A.
- ORCID
- Venue
- Nature Chemical Biology
- Published
- 2022-05-30
- Volume
- 18
- Issue
- 7
- Pages
- 751-761
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC9469796
- OpenAlex
- W4281664411
- Cited by
- 134
- References
- 69
- Citations by year
- 2026: 28 · 2025: 38 · 2024: 29 · 2023: 31 · 2022: 8
- FWCI
- 15.55
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Chemical Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Cancer Society (RSG-19-192-01)
- Melanoma Research Alliance (620458)
- U.S. Department of Health & Human Services | National Institutes of Health (R01GM112948, T32GM007232, F31DK121477, 2T32CA108462, R01CA223817, 1R01GM122923)
- Chan Zuckerberg Biohub, Miller Institute
- United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (W81XWH-18-1-0713)
- Mark Foundation
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Physical Sciences › Chemistry › Organic Chemistry › Organoselenium and organotellurium chemistry
- Keywords
- ribosome stalling, selenoprotein translation, GPX4, ferroptosis, ferroptosis resistance, LRP8, ApoER2, selenocysteine, UGA codon, selenium deficiency, cancer, chemical genetic screen, proteasomal degradation
- MeSH terms
- Ferroptosis, Phospholipid Hydroperoxide Glutathione Peroxidase, Ribosomes, Selenium, Selenoproteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
