Nuclear genes and oxidative phosphorylation disorders: a review

Area of Science:

• Mitochondrial Biology
• Human Genetics
• Molecular Medicine

Background:

• Significant advancements have been made in understanding the ~70 human nuclear genes encoding the core subunits of the oxidative phosphorylation (OXPHOS) system.
• However, knowledge regarding the numerous nuclear genes involved in the regulation, assembly, and quality control of OXPHOS remains limited.
• This gap in knowledge impacts the comprehensive understanding of OXPHOS-related disorders.

Purpose of the Study:

• To review the current state of knowledge regarding nuclear gene mutations in oxidative phosphorylation disorders.
• To highlight the need for further research into regulatory and assembly genes of the OXPHOS system.
• To discuss the potential of genetic strategies in identifying novel gene defects.

Main Methods:

• Review of existing literature on nuclear gene mutations in OXPHOS disorders.
• Discussion of direct genetic strategies, including candidate gene identification.
• Exploration of indirect genetic strategies such as chromosome transfer, linkage analysis, and positional cloning.

Main Results:

• A growing body of knowledge exists for structural nuclear genes of the OXPHOS system.
• A limited number of defects in both structural and non-structural nuclear genes have been identified to date.
• Genetic strategies are expected to accelerate the discovery of genes involved in OXPHOS regulation and assembly.

Conclusions:

• This review summarizes current knowledge on nuclear gene mutations contributing to oxidative phosphorylation disorders.
• Further investigation into regulatory and assembly genes is crucial for a complete understanding of these complex disorders.
• Continued application of genetic techniques will likely expand the identification of causative genes.