NDUFA5

NDUFA5 (NADH:ubiquinone oxidoreductase subunit A5) is a protein subunit of mitochondrial complex I (also known as NADH dehydrogenase or NADH:ubiquinone oxidoreductase). In humans, it is encoded by the NDUFA5 gene. Complex I is the first enzyme complex in the mitochondrial electron transport chain, responsible for the transfer of electrons from NADH to ubiquinone, contributing to the proton gradient across the inner mitochondrial membrane that drives ATP synthesis.

NDUFA5 is a nuclear-encoded subunit of complex I, meaning that its gene is located in the cell nucleus, and the protein is synthesized in the cytoplasm before being imported into the mitochondria. It is considered an accessory subunit, meaning it is not directly involved in the redox reactions or proton translocation that are the core functions of complex I. However, accessory subunits like NDUFA5 play crucial roles in the assembly, stability, and regulation of the entire complex.

The precise function of NDUFA5 within complex I is not fully understood, but research suggests it is involved in the structural integrity of the complex and may play a role in the assembly process. Mutations in the NDUFA5 gene have been linked to mitochondrial disorders, particularly those affecting complex I function, leading to a variety of clinical symptoms including encephalopathy, lactic acidosis, and cardiomyopathy. These disorders highlight the importance of NDUFA5 for proper mitochondrial function and cellular energy production.

Further research is ongoing to fully elucidate the role of NDUFA5 in complex I function and to develop therapeutic strategies for mitochondrial disorders associated with mutations in the NDUFA5 gene.