Ndufa3, also known as NADH: ubiquinone oxidoreductase subunit A3, is a key component of mitochondrial complex I. Mitochondrial complex I is involved in oxidative phosphorylation, a crucial pathway for generating ATP, the energy currency of cells. Ndufa3 is required for the formation of a functional holoenzyme and for the assembly and/or stability of the electron-transferring Q module in the peripheral arm of mitochondrial complex I [4].

In sepsis, high levels of S100a8/a9 can suppress Ndufa3 expression via downregulation of Nrf1, leading to mitochondrial complex I deficiency. This deficiency contributes to Sirt1 suppression, mitochondrial disorders, and ultimately activates ZBP1-mediated PANoptosis in endothelial cells [1]. In human nucleus pulposus cells exposed to high glucose, Ndufa3 overexpression can counteract high-glucose-induced injuries, including suppressing cell apoptosis, eliminating ROS, and improving mitochondrial function. The HDAC/H3K27ac mechanism is involved in regulating Ndufa3 transcription [2]. In a family suspected of having Leigh syndrome, compound heterozygous mutations in the Ndufa3 gene were identified in affected members, suggesting its role in this mitochondrial disorder [3].

In conclusion, Ndufa3 is essential for the proper function of mitochondrial complex I and oxidative phosphorylation. Studies on Ndufa3, especially through genetic mutations as seen in the Leigh syndrome family, have provided insights into its role in mitochondrial-related diseases. Additionally, its regulation and function in conditions like sepsis and high-glucose-induced cell injuries highlight its importance in understanding disease mechanisms and potential therapeutic targets.