Evidence map›Paper›PMID 40846998›Full record

ArticleNature chemical biology2026

α-Ketoglutarate dictates AMPK protein synthesis for energy sensing in human cancers.

Wen Mi, Yun Xue, Haohang Yan, Yurou Zhang, Xinlei Cai, Shuyuan Zhang, Ruiping He, Liucheng Li, Lingzhi Zhu, Xinyi Xia and 12 more

RetractedAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

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  6. GOT2-mediated suppression of CoQCommunications biology · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Wen Mi *Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Yun Xue *School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Haohang YanShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Yurou ZhangShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Xinlei CaiDepartment of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0005-4295-6371
Shuyuan ZhangHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Ruiping HeShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Liucheng LiShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Lingzhi ZhuShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Xinyi XiaShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Yifan LiangShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Chongwen CaoShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Yi XuShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Junfeng BiShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Guanlin WangShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Li ChenShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-8685-3466
Dan YeHuashan Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology) and Molecular and Cell Biology Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-4848-0501
Fei LiDepartment of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Ruobing RenShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-4517-7216
Pingyu LiuHuman Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China.
Hongbin JiSchool of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China.
Fuming LiShanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology; Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China. fuming_li@fudan.edu.cn.ORCID http://orcid.org/0000-0002-2603-1548

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82273223
6 · The paper itself

Abstract

The energy sensor AMP-activated protein kinase (AMPK) promotes tumor cell survival under stress but how to prevent AMPK activation to blunt tumor progression remains unclear. Here we show that the metabolite α-ketoglutarate (α-KG) dictates AMPK translation through a TET-YBX1 axis, which can be exploited to sensitize human cancer cells to energy stress. α-KG-deficient cells fail to activate AMPK under glucose starvation, which elicits cytosolic NADPH depletion and disulfidptosis. Mechanistically, α-KG insufficiency inhibits TET-dependent transcription of YBX1, an RNA-binding protein required for human-specific AMPK protein synthesis. Similarly, α-KG competitors including succinate and itaconate inhibit the YBX1-AMPK axis and sensitize cancer cells to glucose deprivation. Lastly, cotargeting oncogenic YBX1 and GLUT1 creates synthetic lethality and blunts tumor growth in vivo. Together, our findings link α-KG to energy sensing through AMPK translation and propose that targeting α-KG-YBX1-dependent AMPK translation can sensitize human cancer cells to energy stress for treatment.

Indexed as

AMP-Activated Protein KinasesKetoglutaric AcidsNeoplasmsAnimalsCell Line, TumorEnergy MetabolismGlucoseHumansMiceProtein BiosynthesisAMP-Activated Protein KinasesGlucoseKetoglutaric Acids

Identifiers

PMID40846998
PMCPMC12953151

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.