Evidence map›Paper›PMID 39833225›Full record

ArticleNature communications2025

Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis.

Bin Huang, Hui Wang, Shuo Liu, Meng Hao, Dan Luo, Yi Zhou, Ying Huang, Yong Nian, Lei Zhang, Bo Chu and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
–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

106 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Review
  4. Loss of Intestinal MSTN Promotes GLP-1 Secretion Through SGLT1 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Impact of renal iron overload on sickle cell nephropathy in a humanized mouse model.American journal of physiology. Renal physiology · 2026
    Article
  6. Metformin Inhibits Trophoblast Ferroptosis by Suppressing ATF2 and Activating the PI3K/Akt/Nrf2 Pathway to Improve Gestational Diabetes Mellitus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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46 more citing papers are in PubMed but not listed here.

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

11 authors.

Bin Huang *School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Peking University, Shenzhen, Guangdong, China.
Hui Wang *Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Shuo Liu *Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Meng Hao *Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Dan LuoInstitute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Yi ZhouInstitute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Ying HuangInstitute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.
Yong NianCollege of Pharmacy, Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Lei ZhangSchool of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Peking University, Shenzhen, Guangdong, China.ORCID http://orcid.org/0000-0001-5589-5380
Bo ChuDepartment of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.ORCID http://orcid.org/0000-0001-9754-2743
Chengqian YinInstitute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China. yincq@szbl.ac.cn.ORCID http://orcid.org/0000-0003-4247-6245

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

S-palmitoylation is a reversible and widespread post-translational modification, but its role in the regulation of ferroptosis has been poorly understood. Here, we elucidate that GPX4, an essential regulator of ferroptosis, is reversibly palmitoylated on cysteine 66. The acyltransferase ZDHHC20 palmitoylates GPX4 and increases its protein stability. ZDHHC20 depletion or inhibition of protein palmitoylation by 2-BP sensitizes cancer cells to ferroptosis. Moreover, we identify APT2 as the depalmitoylase of GPX4. Genetic silencing or pharmacological inhibition of APT2 with ML349 increases GPX4 palmitoylation, thereby stabilizing the protein and conferring resistance to ferroptosis. Notably, disrupting GPX4 palmitoylation markedly potentiates ferroptosis in xenografted and orthotopically implanted tumor models, and inhibits tumor metastasis through blood vessels. In the chemically induced colorectal cancer model, knockout of APT2 significantly aggravates cancer progression. Furthermore, pharmacologically modulating GPX4 palmitoylation impacts liver ischemia-reperfusion injury. Overall, our findings uncover the intricate network regulating GPX4 palmitoylation, highlighting its pivotal role in modulating ferroptosis sensitivity.

Indexed as

FerroptosisLipoylationPhospholipid Hydroperoxide Glutathione PeroxidaseAcyltransferasesAnimalsCell Line, TumorColorectal NeoplasmsCysteineHumansMicePalmitatesReperfusion Injury2-bromopalmitateAcyltransferasesCysteineglutathione peroxidase 4, mousePalmitatesPhospholipid Hydroperoxide Glutathione Peroxidase

Identifiers

PMID39833225
PMCPMC11746948

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.