Evidence map›Paper›PMID 40275276›Full record

ArticleJournal of translational medicine2025

OPA1 mutations in dominant optic atrophy: domain-specific defects in mitochondrial fusion and apoptotic regulation.

Kexuan Zhang, Wenqing Zhang, Lin Zhang, Xiaorong Hou, Runyi Tian, Zhengmao Hu, Lili Yin, Zhonghua Hu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 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

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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. A combined artificial intelligence-wet lab approach identifies a pivotal role of the NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 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

8 authors.

Kexuan ZhangDepartment of Critical Care Medicine, Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China.
Wenqing ZhangDepartment of Critical Care Medicine, Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China.
Lin ZhangDepartment of Critical Care Medicine, Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China.
Xiaorong HouDepartment of Neurology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Runyi TianCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China.
Zhengmao HuCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China.
Lili YinDepartment of Ophthalmology, Shanghai Fourth People's Hospital, Tongji University, Shanghai, 200434, China. yll1444@alumni.sjtu.edu.cn.
Zhonghua HuDepartment of Critical Care Medicine, Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan, China. huzhonghua@csu.edu.cn.ORCID 0000-0002-0117-7081

Funding

National Natural Science Foundation of China 31872778National Natural Science Foundation of China 82171506
6 · The paper itself

Abstract

backgroundAutosomal dominant optic atrophy (ADOA), a leading common inherited optic neuropathy, arises from progressive retinal ganglion cell degeneration, often linked to OPA1 mutations. OPA1, a mitochondrial GTPase, regulates mitochondrial fusion, crista structure, and apoptosis. While GTPase-related dysfunction is well-studied, the role of other OPA1 domains in ADOA pathology remains unclear.

methodsTo investigate ADOA-linked OPA1 mutations, we assessed mitochondrial morphology, membrane potential, cytochrome c release, and cell viability in primary cortical neurons and N2a cells expressing OPA1 wild-type or mutant constructs. RNA sequencing and structural predictions (SWISS-MODEL) provided insights into molecular pathways and structural impacts.

resultsTwo ADOA-associated mutations were characterized: V465F (GTPase β-fold) and V560F (BSE α-helix). Both mutations impaired mitochondrial fusion and cell survival under apoptotic stimuli. Notably, the BSE-located V560F mutation caused greater deficits in membrane potential maintenance, earlier apoptosis, and distinct molecular pathway changes compared to V465F.

conclusionsThis study highlights the domain-specific impacts of OPA1 mutations on mitochondrial function and ADOA pathology, revealing unique roles of the BSE domain in apoptosis regulation and mitochondrial integrity. These findings provide insights into ADOA mechanisms and potential therapeutic targets.

Indexed as

ApoptosisGTP PhosphohydrolasesMitochondriaMitochondrial DynamicsMutationOptic Atrophy, Autosomal DominantAnimalsCell SurvivalHumansMembrane Potential, MitochondrialMiceModels, MolecularNeuronsProtein DomainsGTP PhosphohydrolasesOPA1 protein, humanOpa1 protein, mouseApoptosisAutosomal dominant optic atrophy (ADOA)Bundle signaling element (BSE)GTPase activityMitochondrial dynamicsOPA1 mutations

Identifiers

PMID40275276
PMCPMC12020257

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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.