Evidence map›Paper›PMID 39120696›Full record

ArticleCellular and molecular life sciences : CMLS2024

Mitochondrial copper overload promotes renal fibrosis via inhibiting pyruvate dehydrogenase activity.

Saiya Zhu, Yangyang Niu, Wenqian Zhou, Yuqing Liu, Jing Liu, Xi Liu, Limin Lu, Chen Yu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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

22 citing papers in PubMed.

  1. Review
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  6. From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
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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

8 authors.

Saiya Zhu *Department of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Yangyang Niu *Department of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Wenqian ZhouDepartment of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Yuqing LiuDepartment of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Jing LiuDepartment of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Xi LiuDepartment of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Limin LuDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Yixueyuan Road, Shanghai, 200032, China. lulimin@shmu.edu.cn.
Chen YuDepartment of Nephrology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. yuchen@tongji.edu.cn.ORCID http://orcid.org/0000-0001-7169-276X

Funding

National Natural Science Foundation of China 82000673National Natural Science Foundation of China 82170696
6 · The paper itself

Abstract

Copper is a trace element essential for numerous biological activities, whereas the mitochondria serve as both major sites of intracellular copper utilization and copper reservoir. Here, we investigated the impact of mitochondrial copper overload on the tricarboxylic acid cycle, renal senescence and fibrosis. We found that copper ion levels are significantly elevated in the mitochondria in fibrotic kidney tissues, which are accompanied by reduced pyruvate dehydrogenase (PDH) activity, mitochondrial dysfunction, cellular senescence and renal fibrosis. Conversely, lowering mitochondrial copper levels effectively restore PDH enzyme activity, improve mitochondrial function, mitigate cellular senescence and renal fibrosis. Mechanically, we found that mitochondrial copper could bind directly to lipoylated dihydrolipoamide acetyltransferase (DLAT), the E2 component of the PDH complex, thereby changing the interaction between the subunits of lipoylated DLAT, inducing lipoylated DLAT protein dimerization, and ultimately inhibiting PDH enzyme activity. Collectively, our study indicates that mitochondrial copper overload could inhibit PDH activity, subsequently leading to mitochondrial dysfunction, cellular senescence and renal fibrosis. Reducing mitochondrial copper overload might therefore serve as a strategy to rescue renal fibrosis.

Indexed as

Cellular SenescenceCopperFibrosisKidneyMitochondriaPyruvate Dehydrogenase ComplexAnimalsCitric Acid CycleDihydrolipoyllysine-Residue AcetyltransferaseHumansKidney DiseasesMaleMiceMice, Inbred C57BLCopperDihydrolipoyllysine-Residue AcetyltransferasePyruvate Dehydrogenase ComplexCopperMitochondriaPyruvate dehydrogenaseRenal fibrosisTricarboxylic acid (TCA) cycle

Identifiers

PMID39120696
PMCPMC11335263

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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.