Mitochondrial disorders of the OXPHOS system
Erika Fernandez-Vizarra1, Massimo Zeviani2,3
1Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
FEBS Letters
|November 7, 2020
Summary
Mitochondrial disorders stem from faulty oxidative phosphorylation (OXPHOS) due to genetic defects in electron transport chain (ETC) assembly. This review covers clinical features and molecular mechanisms of these frequent metabolic diseases.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- Mitochondrial disorders are common inborn errors of metabolism.
- They often result from dysfunction of the oxidative phosphorylation system (OXPHOS).
- OXPHOS involves the electron transport chain (ETC) and ATP synthesis.
Purpose of the Study:
- To review clinical phenotypes of mitochondrial disorders.
- To explore molecular pathological mechanisms.
- Focus on genetic causes related to ETC complex assembly.
Main Methods:
- Literature review of historical and recent findings.
- Analysis of genetic variants impacting ETC component assembly.
- Correlation of genotype with clinical presentation.
Main Results:
- Genetic causes for approximately 50% of diagnosed mitochondrial diseases are identified.
- Pathogenic variants in genes for structural subunits or assembly factors are frequent.
- Disorders arise from impaired OXPHOS and ATP production.
Conclusions:
- Genetic defects in ETC assembly are a major cause of mitochondrial disorders.
- Understanding these mechanisms is crucial for diagnosis and treatment.
- Further research is needed to uncover the genetic basis of remaining cases.
Keywords:
ATP productionbiogenesis of the respiratory chainmitochondrial diseasemitochondrial electrochemical gradientmitochondrial potentialmitochondrial proton pumpingmitochondrial respiratory chainoxidative phosphorylationrespiratory complexrespiratory supercomplexMore Related Videos
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