Ndufs2, also known as NADH dehydrogenase ubiquinone iron-sulfur protein 2, is a core subunit of mitochondrial respiratory chain complex I. Mitochondrial complex I regenerates NAD+ and pumps protons, and Fe-S clusters within it, like the N2 center in Ndufs2, are crucial for electron transfer and play a role in mitochondrial reactive oxygen species (ROS) production. Ndufs2 is involved in many biological processes related to mitochondrial function [2,4].

In dilated cardiomyopathy, loss of lncRNA DCRT leads to PTBP1-mediated exon skipping of Ndufs2, inducing cardiac mitochondrial dysfunction, while coenzyme Q10 can partially alleviate this [1]. In pancreatic cancer, the OTUB1/NDUFS2 axis promotes tumorigenesis by protecting against mitochondrial cell death [2]. Deleting Ndufs2 in lung epithelial cells during mouse gestation causes death during postnatal alveolar development, highlighting the role of Ndufs2-dependent NAD+ regeneration in cell fate determination [3]. Knocking down Ndufs2 in pulmonary artery smooth muscle cells impairs acute oxygen-sensing and hypoxic pulmonary vasoconstriction [5]. In human embryonic kidney cells, disruption of Ndufs2 significantly affects cell growth, metabolism, and apoptosis [6].

In conclusion, Ndufs2 is essential for mitochondrial function, playing a vital role in processes such as cell fate determination during alveolar development, oxygen-sensing in the pulmonary vasculature, and influencing cell growth and apoptosis. Ndufs2 knockout models have revealed its significance in diseases like dilated cardiomyopathy and pancreatic cancer, providing insights into disease mechanisms and potential therapeutic targets.