Evidence map›Paper›PMID 40891328›Full record

ArticleStroke2025

MFN2 and BAG6 Synergistically Protect Against Cerebral Reperfusion Injury by Regulating ROS Levels and Autophagic Flux.

Dongting Lu, Yukun Yang, Guodong Huang, Qinlian Ye, Xingyun Quan, Britta Kaltwasser, Yanfen Liu, Dirk M Hermann, Ulf Brockmeier, Ya-Chao Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. 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

10 authors.

Dongting LuDepartment of Neurology, Guangxi University of Chinese Medicine, Nanning, China (D.L., Y.-C.W.).
Yukun YangDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany (Y.Y., X.Q., B.K., D.M.H., U.B.).
Guodong HuangDepartment of Neurosurgery, Institute of Translational Medicine, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University, China (G.H., Q.Y., Y.-C.W.).
Qinlian YeDepartment of Neurosurgery, Institute of Translational Medicine, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University, China (G.H., Q.Y., Y.-C.W.).ORCID 0009-0008-6864-0174
Xingyun QuanDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany (Y.Y., X.Q., B.K., D.M.H., U.B.).
Britta KaltwasserDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany (Y.Y., X.Q., B.K., D.M.H., U.B.).
Yanfen LiuSchool of Life Science and Technology, ShanghaiTech University, China (Y.L.).ORCID 0000-0002-1192-8328
Dirk M HermannDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany (Y.Y., X.Q., B.K., D.M.H., U.B.).ORCID 0000-0003-0198-3152
Ulf BrockmeierDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Germany (Y.Y., X.Q., B.K., D.M.H., U.B.).
Ya-Chao WangDepartment of Neurology, Guangxi University of Chinese Medicine, Nanning, China (D.L., Y.-C.W.).ORCID 0000-0003-3709-5368

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMFN2 (mitofusin-2), a transmembrane dynamin-like protein located on the outer mitochondrial membrane, plays a key role in regulating mitochondrial fusion and autophagy. In vitro studies suggested that MFN2 may exert neuroprotective effects postischemia. In gain-of-function and loss-of-function experiments, we investigated MFN2'·s roles in regulating neuronal ischemia/reperfusion injury in vivo and in vitro.

methodsMFN2 was knocked down by neuron-specific conditional knockout or siRNA-mediated knockdown and overexpressed by adeno-associated viral vectors or plasmid vectors in C57BL/6 mice of both sexes (10-12 weeks) exposed to middle cerebral artery occlusion and SY5Y cells exposed to oxygen-glucose deprivation/reoxygenation. Neurological deficits were examined using a 48-point score and rotarod tests. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride staining. A RealTime Apoptosis and Necrosis Assay was used to measure apoptotic and necrotic cell death. Reactive oxygen species (ROS) formation and autophagic flux were analyzed by functional assays. Protein expression and interaction were evaluated using Western blots, immunoaffinity chromatography, mass spectrometry, and immunoprecipitation analysis. To assess the role of MFN2's interaction partner BAG6, BAG6 was overexpressed in middle cerebral artery occlusion mice and overexpressed or knocked down in SY5Y cells.

resultsNeuron-specific MFN2 deletion exacerbated cerebral ischemia/reperfusion injury, while MFN2 overexpression reduced it. MFN2 deficiency elevated mitochondrial ROS levels and inhibited autophagy, whereas MFN2 overexpression decreased ROS levels. In immunoprecipitation studies, we found a direct interaction between MFN2 and BAG6. Of note, BAG6 overexpression mimicked the effect of MFN2 overexpression on cerebral ischemia/reperfusion injury. Combined MFN2 and BAG6 overexpression synergistically reduced ischemia/reperfusion injury by drastically decreasing cerebral ROS levels, stabilizing mitochondrial function, and modulating autophagy.

conclusionsOur study suggests that MFN2 enhances stroke outcome through 2 pathways: by decreasing ROS levels and modulating autophagy via interaction with BAG6. BAG6 potentiates the ROS-lowering, cytoprotective MFN2 actions. The MFN2-BAG6 axis represents a promising target for stroke therapy.

Indexed as

Adaptor Proteins, Signal TransducingAutophagyGTP PhosphohydrolasesMitochondrial ProteinsReactive Oxygen SpeciesReperfusion InjuryAnimalsFemaleHumansInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLMice, KnockoutAdaptor Proteins, Signal TransducingGTP PhosphohydrolasesMfn2 protein, mouseMitochondrial ProteinsReactive Oxygen Speciesautophagyglucoseinfarction, middle cerebral arteryischemic stroketriphenyltetrazolium

Identifiers

PMID40891328
PMCPMC12643567

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.