Evidence map›Paper›PMID 40988976›Full record

ArticleResearch (Washington, D.C.)2025

LHPP Attenuates Lipid Dysfunction of Uveal Melanoma by Relieving the Histidine Phosphorylation of ACO2.

Zhi Yang, Liang Ma, Yidian Fu, Xiaoyu He, Yingxiu Luo, Shengfang Ge, Renbing Jia, Jian Huang, Xianqun Fan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Research (Washington, D.C.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Review
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

9 authors.

Zhi YangState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.ORCID https://orcid.org/0000-0001-9440-7896
Liang MaState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Yidian FuState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Xiaoyu HeState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Yingxiu LuoState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Shengfang GeState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Renbing JiaState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Jian HuangDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Xianqun FanState Key Laboratory of Eye Health, Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Histidine phosphorylation, the neglected but vital phosphoproteome, is a reversible posttranslational modification catalyzed by histidine kinases and erased by phosphohistidine (pHis) phosphatases (e.g., LHPP). Traditional types of phosphorylation have been implicated with the deadliest adult ocular tumor uveal melanoma (UM), which is lipid metabolism dysfunction related. However, the role of histidine phosphorylation in UM remains unknown. Here, up-regulated histidine phosphorylation is associated with poor UM prognosis. Reversal of histidine phosphorylation by LHPP exerts therapeutic effects. Mechanistically, we identified LHPP as metabolically related protein with mitochondrial targeting sequence. LHPP interacts and reduces excessive histidine phosphorylation of mitochondrial aconitase ACO2 at H73 site, thus restoring ACO2 enzymatic activity and mitochondrial citrate transit in TCA cycle. Reduction of citrate accumulation attenuates overloaded lipid synthesis. Besides, genetic ablation of LHPP in mouse eye exhibits abnormal lipid metabolism. These findings illustrate the antagonistic roles of oncogenic histidine phosphorylation and therapeutic mitochondrial LHPP and provide metabolic insight of pHis modification in ocular diseases.

Identifiers

PMID40988976
PMCPMC12451111

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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.