Evidence map›Paper›PMID 34429398›Full record

ArticleCell death & disease2021

SESN2 protects against denervated muscle atrophy through unfolded protein response and mitophagy.

Xiaofan Yang, Pingping Xue, Meng Yuan, Xiang Xu, Cheng Wang, Wenqing Li, Hans-Günther Machens, Zhenbing Chen

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. 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
2.0field-weighted citation impact, top 12% of its field
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, 36 citations in OpenAlex.

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  13. Deletion of Transferrin Receptor 1 in Parvalbumin Interneurons Induces a Hereditary Spastic Paraplegia-Like Phenotype.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
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  18. Sestrin2 in diabetes and diabetic complications.Frontiers in endocrinology · 2023
    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 at 3 institutions in 2 countries.

Xiaofan YangDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Pingping XueDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Meng YuanDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xiang XuDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cheng WangDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Wenqing LiDepartment of Hand and Foot Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, China.
Hans-Günther MachensDepartment of Plastic and Hand Surgery, Technical University of Munich, Munich, 81675, Germany.
Zhenbing ChenDepartment of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. zbchen@hust.edu.cn.ORCID 0000-0003-2828-866X
Union Hospital · CNTechnical University of Munich · DETongji Hospital · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81471270National Natural Science Foundation of China (National Science Foundation of China) 81772094National Natural Science Foundation of China (National Science Foundation of China) 81974289
6 · The paper itself

Abstract

Denervation of skeletal muscles results in a rapid and programmed loss of muscle size and performance, termed muscle atrophy, which leads to a poor prognosis of clinical nerve repair. Previous researches considered this process a result of multiple factors, such as protein homeostasis disorder, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis, while their intrinsic association remains to be explored. In this study, Sestrin2 (SESN2), a stress-inducible protein, was shown to act as a key protective signal involved in the crosstalk therein. SESN2 expression was induced in the gastrocnemius two weeks post denervation, which was accompanied by ERS, mitochondrial dysfunction, and apoptosis. Knockdown of SESN2 aggravated this situation and resulted in severer atrophy. Similar results were also found in rotenone-treated C2C12 cells. Furthermore, SESN2 was demonstrated to be induced by an ERS-activated transcription factor CCAAT-enhancer-binding protein beta (C/EBPβ). Once induced, SESN2 halted protein synthesis by inhibiting the mammalian target of rapamycin complex 1 (mTORC1), thereby attenuating ERS. Moreover, increased SESN2 activated the specific autophagic machinery and facilitated the aggregation of sequestosome 1 (SQSTM1, p62) on the mitochondrial surface, which promoted the clearance of damaged mitochondria through mitophagy. Collectively, the SESN2-mediated unfolded protein response (UPR) and mitophagy play a critical role in protecting against denervated muscle atrophy, which may provide novel insights into the mechanism of skeletal muscle atrophy following denervation.

Indexed as

DenervationMitophagyUnfolded Protein ResponseAdenylate KinaseAnimalsApoptosisBase SequenceCCAAT-Enhancer-Binding Protein-betaCell LineeIF-2 KinaseEndoplasmic Reticulum StressGene Knockdown TechniquesMaleMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLAdenylate KinaseCCAAT-Enhancer-Binding Protein-betaCebpb protein, mouseeIF-2 KinaseMechanistic Target of Rapamycin Complex 1PeroxidasesProtective AgentsRotenoneSesn2 protein, mouseSestrins

Identifiers

PMID34429398
PMCPMC8384848
OpenAlexW3194888011

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.