Evidence map›Paper›PMID 42169250›Full record

ArticleAutophagy2026

UCHL3 drives ferroptosis in nucleus pulposus cells by deubiquitinating HMGB1 to activate NCOA4-mediated ferritinophagy.

Tao Hu, Peng Cui, Xuan Zhao, Wei Wang, Yingdong Ma, Xinli Hu, Haojie Zhang, Zuoran Fan, Dongfan Wang, Qingyang Huang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Tao HuDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Peng CuiDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Xuan ZhaoDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Wei WangDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Yingdong MaSchool of Pharmaceutical Sciences, Laboratory for Clinical Medicine, Capital Medical University, Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China.
Xinli HuDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Haojie ZhangDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Zuoran FanDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Dongfan WangDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Qingyang HuangDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Fumin PanDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Haixia HuangDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Chunying CuiSchool of Pharmaceutical Sciences, Laboratory for Clinical Medicine, Capital Medical University, Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China.
Xiaolong ChenDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
Yuluo RongDepartment of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Shibao LuDepartment of Orthopaedics, Xuanwu Hospital, Capital Medical University, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ferroptosis contributes to intervertebral disc degeneration (IVDD), yet its upstream regulatory mechanisms in nucleus pulposus cells (NPCs) remain unclear. Here, we identify a novel UCHL3-HMGB1-NCOA4 signaling axis that drives NPC ferroptosis. Transcriptomic and clinical analyses reveal that UCHL3 is upregulated in degenerative discs, with its expression correlating positively with both IVDD severity and ferroptosis markers. Mechanistically, UCHL3 deubiquitinates and stabilizes HMGB1 by cleaving Lys48-linked polyubiquitin chains, thereby promoting the accumulation of cytoplasmic HMGB1. This stabilized HMGB1 activates NCOA4-mediated ferritinophagy, initiating ferroptosis. Silencing

Indexed as

FerroptosisHMGB1 ProteinNuclear Receptor CoactivatorsNucleus PulposusUbiquitin ThiolesteraseAnimalsHumansIntervertebral Disc DegenerationMaleRatsRats, Sprague-DawleyUbiquitinationHMGB1 ProteinNCOA4 protein, humanNuclear Receptor CoactivatorsUbiquitin ThiolesteraseDeubiquitinationferritinophagyferroptosisintervertebral disc degenerationnucleus pulposus cellUCHL3

Identifiers

PMID42169250
PMCPMC13618859

What OpenQuestion holds

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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.