NDUFA3 is a supernumerary accessory subunit of mitochondrial respiratory chain Complex I (NADH dehydrogenase) required for proper assembly and function of the electron-transferring Q module in the peripheral arm 1. While not directly involved in catalysis, NDUFA3 is essential for transferring electrons from NADH to ubiquinone and maintaining the proton motive force for ATP synthesis [UniProt]. Loss of NDUFA3 expression impairs mitochondrial function, increasing reactive oxygen species production, reducing oxygen consumption rates, and decreasing mitochondrial membrane potential 2. Clinically, NDUFA3 mutations cause Leigh syndrome, a severe early-onset mitochondrial disorder presenting with motor developmental delay, muscle tone abnormalities, and characteristic basal ganglia/brainstem lesions 34. NDUFA3 expression is suppressed during sepsis through S100A8/A9-mediated downregulation of Nrf1, contributing to endothelial dysfunction and PANoptosis 5. In diabetes-induced intervertebral disc degeneration, HDAC/H3K27ac-mediated NDUFA3 transcription upregulation protects nucleus pulposus cells by restoring mitochondrial oxidative phosphorylation 2. Additionally, NDUFA3 is part of a validated 5-gene peripheral blood signature predicting immunotherapy response in non-small cell lung cancer 6.