Evidence map›Paper›PMID 42457680›Full record

ArticleNature communications2026

The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.

Dejun Xu, Shuaifei Song, Qingmiao Shi, Zhiling Zhao, Wenhao Zhao, Lei Wang, Guangxin E, Yanguo Han, Yongju Zhao, Zhongquan Zhao

Abstract read
In one paragraph

Article in Nature communications, 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

10 authors.

Dejun Xu *College of Animal Science and Technology, Southwest University, Chongqing, China.ORCID http://orcid.org/0000-0002-5407-7359
Shuaifei Song *College of Animal Science and Technology, Southwest University, Chongqing, China.
Qingmiao ShiCollege of Animal Science and Technology, Southwest University, Chongqing, China.
Zhiling ZhaoCollege of Animal Science and Technology, Southwest University, Chongqing, China.
Wenhao ZhaoCollege of Animal Science and Technology, Southwest University, Chongqing, China.
Lei WangCollege of Animal Science and Technology, Southwest University, Chongqing, China.
Guangxin ECollege of Animal Science and Technology, Southwest University, Chongqing, China.
Yanguo HanCollege of Animal Science and Technology, Southwest University, Chongqing, China.
Yongju ZhaoCollege of Animal Science and Technology, Southwest University, Chongqing, China.
Zhongquan ZhaoCollege of Animal Science and Technology, Southwest University, Chongqing, China. zhaozhongquan@swu.edu.cn.ORCID http://orcid.org/0000-0002-6268-8539

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32102623
6 · The paper itself

Abstract

Mitochondrial dysfunction and epigenetic alterations play critical roles in aging-related diseases, yet the molecular mechanisms linking mito-nuclear crosstalk to ovarian aging remain poorly understood. Here, single-cell transcriptome analysis of aging ovaries revealed senescence-associated hallmark alterations, including abnormally elevated mitochondrial metabolism, disrupted histone modification patterns, and enrichment of the senescence-associated secretory phenotype (SASP). We demonstrated that impaired SIRT5-mediated desuccinylation constitutes a key driver of ovarian aging. Mechanistically, we identified succinyl-coenzyme A (CoA) synthetase GDP-forming subunit β (SUCLG2) in the tricarboxylic acid (TCA) cycle as the main target of SIRT5-mediated desuccinylation. SUCLG2 desuccinylation at lysine residues K93 and K101 enhanced its protein stability and activity, thereby improving mitochondrial function upon cellular senescence. However, SUCLG2 hypersuccinylation specifically increased H4K8ac through acetyl-CoA accumulation in nucleus, leading to the overexpression of metabolism-related genes to compensate for the energy demand deficiency caused by decreased mitochondrial function during cellular senescence. In vivo functional studies demonstrated that acetyl-CoA oversupply accelerated ovarian aging, whereas ovarian gene therapy employing a SUCLG2 desuccinylation mutant ameliorated this condition. This study illuminates the molecular mechanisms underlying ovarian aging and identifies the SIRT5-SUCLG2 axis as a promising therapeutic target for age-related ovarian dysfunction.

Indexed as

AgingEpigenesis, GeneticMitochondriaOvarySirtuinsSuccinate-CoA LigasesAnimalsCellular SenescenceCitric Acid CycleFemaleHistonesHumansMiceHistonesSIRT5 protein, humanSirtuinsSuccinate-CoA Ligases

Identifiers

PMID42457680
PMCPMC13490516

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.