PUBLICATION
A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function
- Authors
- Li, T., Aziz, T., Li, G., Zhang, L., Yao, J., Jia, S.
- ID
- ZDB-PUB-240603-3
- Date
- 2024
- Source
- Journal of genetics and genomics = Yi chuan xue bao 51(9): 922-933 (Journal)
- Registered Authors
- Jia, Shunji, Li, Ting, Yao, Jihua
- Keywords
- COXPD4, Disease model, Mitochondria, Tufm, Zebrafish
- MeSH Terms
-
- Humans
- Oxidative Phosphorylation
- Mitochondrial Diseases*/genetics
- Mitochondrial Diseases*/pathology
- Animals
- Mitochondria*/genetics
- Mitochondria*/metabolism
- Mitochondria*/pathology
- Zebrafish*/genetics
- Disease Models, Animal*
- Mutation*/genetics
- Citric Acid Cycle/genetics
- Mitochondrial Proteins/genetics
- Mitochondrial Proteins/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38825039 Full text @ J. Genet. Genomics
Citation
Li, T., Aziz, T., Li, G., Zhang, L., Yao, J., Jia, S. (2024) A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function. Journal of genetics and genomics = Yi chuan xue bao. 51(9):922-933.
Abstract
Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular energy. Mutations in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4 (COXPD4), a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain (MRC) complexes. The development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical management. In this study, we construct a zebrafish tufm-/- mutant that closely resembles the COXPD4 syndrome, exhibiting compromised mitochondrial protein translation, dysfunctional mitochondria with oxidative phosphorylation (OXPHOS) defects, and significant metabolic suppression of the tricarboxylic acid (TCA) cycle. Leveraging this COXPD4 zebrafish model, we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing COXPD4. Our data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping