NDUFS3, or NADH dehydrogenase [ubiquinone] ferrithionein 3, is a non-catalytic core subunit of mitochondrial respiratory chain Complex I (CI) [3]. CI is crucial for the energy production of the cell, thus NDUFS3 is essential in maintaining normal mitochondrial function and energy metabolism. It may be involved in pathways related to oxidative phosphorylation and plays an overall significant role in cell survival and function [4]. Genetic models, such as knockout models, are valuable for studying its function.

In a study on sepsis-induced acute kidney injury (SI-AKI), overexpression of NDUFS3 inhibited LPS-induced ferroptosis and mitochondrial damage in HK-2 cells, and it exerted a protective role through the AMPK pathway [1]. In atherosclerosis and chronic stress, NDUFS3 was underexpressed, and lower levels were associated with a worse prognosis [2]. In the context of Parkinson's disease in a PINK1B9 Drosophila model, down-regulation of NDUFS3 gene expression may have a protective effect, potentially related to reducing oxidative stress and restoring mitochondrial function [5].

In conclusion, NDUFS3 is vital for mitochondrial function and energy metabolism. Model-based research, including the use of Drosophila models, has revealed its role in various disease conditions such as SI-AKI, atherosclerosis, and Parkinson's disease. Understanding NDUFS3 provides insights into the underlying mechanisms of these diseases and may offer potential therapeutic targets.