Evidence map›Paper›PMID 39350223›Full record

ArticleJournal of experimental & clinical cancer research : CR2024

Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling.

Xiaodong Li, Jingjing Tie, Yuze Sun, Chengrong Gong, Shizhou Deng, Xiyu Chen, Shujiao Li, Yaoliang Wang, Zhenhua Wang, Feifei Wu and 6 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Mitophagy coordinates organelle crosstalk in health and diseases.Signal transduction and targeted therapy · 2026
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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

16 authors.

Xiaodong Li *Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China.
Jingjing Tie *Specific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China.
Yuze Sun *Department of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Chengrong Gong *Department of Computer Fundamentals, The Fourth Military Medical University, Xi'an, 710032, China.
Shizhou DengDepartment of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Xiyu ChenDepartment of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Shujiao LiSpecific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China.
Yaoliang WangDepartment of Neurosurgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Zhenhua WangDepartment of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
Feifei WuSpecific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China.
Hui LiuSpecific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China.
Yousheng WuSpecific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China.
Guopeng ZhangDepartment of Computer Fundamentals, The Fourth Military Medical University, Xi'an, 710032, China. zhanggp@fmmu.edu.cn.ORCID http://orcid.org/0009-0004-9577-1904
Qingdong GuoDepartment of Neurosurgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China. guoqd1991@sina.cn.ORCID http://orcid.org/0000-0002-6914-637X
Yanling YangDepartment of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi'an, 710032, China. yangyanl@fmmu.edu.cn.ORCID http://orcid.org/0000-0001-8246-1756
Yayun WangSpecific Lab for Mitochondrial Plasticity Underlying Nervous System Diseases, National Demonstration Center for Experimental Preclinical Medicine Education, The Fourth Military Medical University, Xi'an, 710032, China. wangyy@fmmu.edu.cn.ORCID http://orcid.org/0000-0002-0397-0390

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe dynamics of mitochondrial respiratory cristae (MRC) and its impact on oxidative phosphorylation (OXPHOS) play a crucial role in driving the progression of high-grade glioma (HGG). However, the underlying mechanism remains unclear.

methodsIn the present study, we employed machine learning-based transmission electron microscopy analysis of 7141 mitochondria from 54 resected glioma patients. Additionally, we conducted bioinformatics analysis and multiplex immunohistochemical (mIHC) staining of clinical glioma microarrays to identify key molecules involved in glioma. Subsequently, we modulated the expression levels of mitochondrial dynamic-1-like protein (DNM1L/DRP1), and its two receptors, mitochondrial fission protein 1 (FIS1) and mitochondrial fission factor (MFF), via lentiviral transfection to further investigate the central role of these molecules in the dynamics of glioblastoma (GBM) cells and glioma stem cells (GSCs). We then evaluated the potential impact of DNM1L/DRP1, FIS1, and MFF on the proliferation and progression of GBM cells and GSCs using a combination of CCK-8 assay, Transwell assay, Wound Healing assay, tumor spheroid formation assay and cell derived xenograft assay employing NOD/ShiLtJGpt-Prkdc

resultsOur findings revealed that compared to low-grade glioma (LGG), HGG exhibited more integrated MRC structures. Further research revealed that DNM1L/DRP1, FIS1, and MFF played pivotal roles in governing mitochondrial fission and remodeling MRC in HGG. The subsequent validation demonstrated that DNM1L/DRP1 exerts a positive regulatory effect on FIS1, whereas the interaction between MFF and FIS1 demonstrates a competitive inhibition relationship. The down-regulation of the DNM1L/DRP1-FIS1 axis significantly impaired mitophagy, thereby hindering the remodeling of MRC and inhibiting OXPHOS function in glioma, ultimately leading to the inhibition of its aggressive progression. In contrast, MFF exerts a contrasting effect on MRC integrity, OXPHOS activity, and glioma progression.

conclusionsThis study highlights that the DNM1L/DRP1-FIS1 axis stabilizes MRC structures through mitophagy in HGG cells while driving their OXPHOS activity ultimately leading to robust disease progression. The inhibition of the DNM1L/DRP1-FIS1 axis hinders MRC remodeling and suppresses GBM progression. We propose that down-regulation of the DNM1L/DRP1-FIS1 axis could be a potential therapeutic strategy for treating HGG.

Indexed as

Disease ProgressionDynaminsGliomaMitochondriaMitochondrial ProteinsAnimalsBrain NeoplasmsCell Line, TumorCell ProliferationFemaleGTP PhosphohydrolasesHumansMaleMembrane ProteinsMiceMitochondrial DynamicsDNM1L protein, humanDynaminsFIS1 protein, humanGTP PhosphohydrolasesMembrane ProteinsMitochondrial ProteinsDNM1L/DRP1FIS1GliomaMitochondrial respiratory cristaeMitophagyOXPHOS

Identifiers

PMID39350223
PMCPMC11440692

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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.