PUBLICATION
Mitochondrial dysfunction is driven by imbalanced fission and fusion of mitochondria in myofibrillar myopathy type 5
- Authors
- Wu, W., Lv, X., Feng, Y., Yang, M., Yang, G., Zhao, D., Yan, C., Lin, P.
- ID
- ZDB-PUB-250418-7
- Date
- 2025
- Source
- Human molecular genetics : (Journal)
- Registered Authors
- Keywords
- filamin-C, mitochondria, mitochondrial dynamics, myofibrillar myopathy
- MeSH Terms
-
- Filamins*/genetics
- Filamins*/metabolism
- Humans
- Mitophagy/genetics
- Mitochondrial Dynamics*/genetics
- Animals
- Mitochondria*/genetics
- Mitochondria*/metabolism
- Mitochondria*/pathology
- Zebrafish/genetics
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology
- Disease Models, Animal
- Mutation
- Myopathies, Structural, Congenital*/genetics
- Myopathies, Structural, Congenital*/metabolism
- Myopathies, Structural, Congenital*/pathology
- PubMed
- 40244302 Full text @ Hum. Mol. Genet.
Citation
Wu, W., Lv, X., Feng, Y., Yang, M., Yang, G., Zhao, D., Yan, C., Lin, P. (2025) Mitochondrial dysfunction is driven by imbalanced fission and fusion of mitochondria in myofibrillar myopathy type 5. Human molecular genetics. :.
Abstract
Myofibrillar myopathy type 5 (MFM5) is a dominantly inherited myopathy caused by mutations in the FLNC gene. The underlying pathogenic mechanisms of MFM5 remain unclear, and there are currently no effective treatments available. This study hypothesizes that mitochondrial dysfunction plays a key role in the pathogenesis of MFM5, on the basis of the COX-negative fibres observed in MFM5 patients. To test this hypothesis, a zebrafish model was developed to explore the impact of filamin-C on mitochondrial dynamics. These results demonstrated that defects in filamin-C disrupt mitochondrial fission, leading to mitochondrial dysfunction and mitophagy. This hypothesis was further validated through the analysis of skeletal muscle samples from MFM5 patients. These findings suggest that mitochondrial dysfunction caused by imbalanced fission and fusion of mitochondria and mitophagy contributes to MFM5 pathology. Importantly, this study identified potential therapeutic targets for MFM5 treatment, opening avenues for future research aimed at developing targeted interventions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping