NDUFS4

NDUFS4 is a gene that encodes one of the subunits of NADH dehydrogenase (ubiquinone) Fe-S protein 4, a component of the mitochondrial respiratory chain that catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the third step of oxidative phosphorylation. This process is crucial for the production of adenosine triphosphate (ATP), the main energy source for many cellular processes.

Function

The NDUFS4 gene is located on the short (p) arm of chromosome 5 at position 13.1. The protein it encodes is a subunit of the Complex I (NADH:ubiquinone oxidoreductase), the first enzyme complex in the mitochondrial respiratory chain. It is involved in the transfer of electrons from NADH to ubiquinone, a process that is coupled with proton translocation across the mitochondrial inner membrane. This results in the generation of a proton gradient, which drives ATP synthesis.

Clinical significance

Mutations in the NDUFS4 gene are associated with Leigh syndrome, a severe neurological disorder that typically arises in the first year of life. Affected individuals may suffer from a variety of symptoms, including loss of previously acquired motor skills, loss of appetite, vomiting, and seizures. In most cases, the disease is fatal within a few years.

Leigh syndrome due to NDUFS4 deficiency is inherited in an autosomal recessive manner, meaning that an individual must have two copies of the mutated gene to develop the disease. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Research

Research into NDUFS4 and its role in mitochondrial function and disease is ongoing. Studies have shown that knockout of the NDUFS4 gene in mice results in a phenotype similar to Leigh syndrome, providing a valuable model for studying the disease. Other research is focused on developing therapies for NDUFS4-related Leigh syndrome, including gene therapy and pharmacological approaches.