Evidence map›Paper›PMID 40844875›Full record

ArticleCell reports2025

TCF25 serves as a nutrient sensor to orchestrate metabolic adaptation and cell death by enhancing lysosomal acidification under glucose starvation.

Wenqing Ren, Hui Jiang, Qianqian Song, Yiliang Chen, Chenxiao Tang, Fang Wang, Jing Zhu, Jingming Ren, Yaxing Zhao, Yuan He and 11 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Bayesian Genome-Wide Association Study of Feed Efficiency Traits in Pigs.Animals : an open access journal from MDPI · 2026
    Article
  2. Review
  3. Prenatal diagnosis and genetic counseling of aThe Journal of international medical research · 2026
    Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Wenqing RenTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: 2205378@tongji.edu.cn.
Hui JiangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Qianqian SongTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Yiliang ChenTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Chenxiao TangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Fang WangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Jing ZhuTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Jingming RenTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Yaxing ZhaoTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Yuan HeTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Jin CaiTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Tianle ZhangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Zhuhong WangTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Chenjie ZhuDepartment of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China.
Wen XueCenter for Nephrology & Metabolomics, Division of Nephrology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Ai PengCenter for Nephrology & Metabolomics, Division of Nephrology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
Xiaona FengCollege of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, Yinchuan 750004, China.
Yue LiuCollege of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, Yinchuan 750004, China.
Jianqiang YuCollege of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, Yinchuan 750004, China.
Zheng-Gang LiuLaboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Zhenyu CaiTongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai 200331, China; College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, Yinchuan 750004, China; State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China. Electronic address: drcaizhenyu@tongji.edu.cn.

Funding

Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

Cells adapt to nutrient limitation by activating catabolic and inhibiting anabolic pathways, yet prolonged stress may lead to cell death. How cells orchestrate metabolic adaptation and cell death to nutrient stress is poorly understood. We conduct a genome-wide CRISPR-Cas9 screen to identify regulators in glucose-starvation-induced cell death and find a group of genes in lysosomal pathway is enriched following glucose starvation. We focus on one candidate gene, Transcriptional Factor 25 (TCF25). We find TCF25 enhances lysosomal acidification by targeting V-ATPase, promoting autophagy and ATP generation under glucose starvation. However, prolonged glucose starvation constitutively activates ferritinophagy via TCF25, increasing lysosomal membrane permeability (LMP) and leading to lysosome-dependent cell death (LDCD). Knocking out TCF25 or V-ATPase components prevents cell death. Furthermore, TCF25 deficiency protects mice from hepatic ischemia-reperfusion injury. Our findings identify TCF25 as a crucial nutrient sensor that regulates lysosomal activity, offering potential therapeutic targets for metabolic and ischemic disorders.

Indexed as

Adaptation, PhysiologicalBasic Helix-Loop-Helix ProteinsGlucoseLysosomesNutrientsTranscription FactorsAnimalsAutophagyCell DeathHumansMiceMice, Inbred C57BLReperfusion InjuryVacuolar Proton-Translocating ATPasesBasic Helix-Loop-Helix ProteinsGlucoseNutrientsTranscription FactorsVacuolar Proton-Translocating ATPasescell deathCP: Cell biologyCP: Metabolismglucose starvationlysosomemetabolic adaptationTCF25

Identifiers

PMID40844875
PMCPMC13010378

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.