NADH Dehydrogenase 1 Alpha Subcomplex 4 (NDUFA4) is a crucial component of the mitochondrial respiratory chain, specifically associated with Complex IV. This enzyme plays a vital role in cellular energy metabolism by participating in the electron transport chain, which is essential for the production of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS).
NDUFA4 is encoded by the NDUFA4 gene located on human chromosome 7p21.3 . The protein is composed of 81 amino acids and is integral to the mitochondrial inner membrane. It functions as a part of the larger NADH dehydrogenase complex, facilitating the transfer of electrons from NADH to the respiratory chain .
NDUFA4 is essential for the proper functioning of the mitochondrial respiratory chain. It is involved in NADH dehydrogenase and oxidoreductase activities, transferring electrons from NADH to the respiratory chain. This process drives oxidative phosphorylation and is crucial for ATP production, respiratory electron transport, chemiosmotic coupling to ATP synthesis, and the generation of heat through the uncoupling of proteins .
Alterations in the expression and function of NDUFA4 have been implicated in various diseases, including cancer. For instance, aberrant expression of NDUFA4 has been linked to gastrointestinal cancers such as colorectal, liver, and gastric cancers . The protein’s role in mitochondrial energy metabolism makes it a potential target for therapeutic interventions in these diseases.
Human recombinant NDUFA4 is produced using recombinant DNA technology, which involves inserting the human NDUFA4 gene into a suitable expression system, such as bacteria or yeast. This allows for the large-scale production of the protein for research and therapeutic purposes. Recombinant NDUFA4 is used in various studies to understand its function, structure, and role in disease, as well as to develop potential treatments targeting mitochondrial dysfunctions.