Evidence map›Paper›PMID 41666677›Full record

ArticleRedox biology2026

Src-mediated PHB2 phosphorylation disrupts mitochondrial cristae through cardiolipin dissociation in hepatocellular carcinoma.

Zhehua Shao, Xinnuo Yang, Binben Wang, Xuwen Wang, Duoduo Zhao, Bingchen Liu, Jinliang Nan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

7 authors.

Zhehua ShaoKey Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address: shaozhehua@zju.edu.cn.
Xinnuo YangDepartment of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Binben WangSchool of Mathematical Sciences, Zhejiang University, Hangzhou, China.
Xuwen WangCollege of Information Science and Electronic Engineering, Zhejiang University, Hangzhou, China.
Duoduo ZhaoBone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Bingchen LiuDepartment of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, China; Research Center for Life Science and Human Health, Binjiang Institute of Zhejiang University, Hangzhou, China. Electronic address: liubingchen111@zju.edu.cn.
Jinliang NanDepartment of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, China; Research Center for Life Science and Human Health, Binjiang Institute of Zhejiang University, Hangzhou, China. Electronic address: jinliangnan@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) displays mitochondrial dysfunction characterized by disrupted redox homeostasis and cristae disorganization, yet the underlying molecular mechanisms are unclear. We reveal that Src kinase phosphorylates prohibitin 2 (PHB2) at tyrosines Y34 and Y77 under oxidative stress, disrupting its interaction with cardiolipin and triggering PHB1/2 complex disassembly. This event activates the mitochondrial protease OMA1, promoting excessive cleavage of the cristae-shaping protein OPA1, leading to severe cristae remodeling. Consequent impairment of electron transport chain supercomplexes decreases NAD+/NADH ratio and complex I/II activities, creating conditions that promote enhanced electron leakage and oxidative stress. This mitochondrial dysfunction drives a metabolic shift from oxidative phosphorylation toward glycolysis, promoting tumor growth in xenograft models. Phosphomimetic PHB2 mutants (Y34E/Y77E) exacerbate these effects, whereas phosphorylation-resistant mutants (Y34F/Y77F) restore cristae integrity, normalize redox balance, and suppress tumor progression. Our findings establish Src-mediated PHB2 phosphorylation as a redox-sensitive molecular switch that drives HCC metabolic reprogramming by disrupting the PHB2-cardiolipin cristae axis. This phosphorylation event represents a targetable vulnerability for this malignancy with limited treatment options.

Indexed as

Carcinoma, HepatocellularCardiolipinsLiver NeoplasmsMitochondriaRepressor Proteinssrc-Family KinasesAnimalsCell Line, TumorHumansMetabolic ReprogrammingMiceOxidative StressPhosphorylationProhibitinsCardiolipinsPHB2 protein, humanPhb2 protein, mouseProhibitinsRepressor Proteinssrc-Family KinasesCardiolipinHepatocellular carcinoma (HCC)Mitochondrial cristaeProhibitinRedox homeostasisSrc-mediated phosphorylation

Identifiers

PMID41666677
PMCPMC12914208

What OpenQuestion 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 OpenQuestion graph.