Ndufs1-flox Mouse

Ndufs1, also known as NADH:ubiquinone oxidoreductase core subunit S1, is a key component of mitochondrial complex I. It plays a crucial role in oxidative phosphorylation (OXPHOS), facilitating the transfer of electrons from NADH to ubiquinone, which is essential for ATP production. This process is integral to maintaining normal cellular energy metabolism and mitochondrial function [2,3,7].

In various disease models, Ndufs1 has shown significant impacts. In myocardial infarction mouse models, cardiac-specific overexpression of Ndufs1 alleviated cardiac dysfunction and fibrosis, reducing ROS production and apoptosis, and improving complex I activity and mitochondrial respiratory function [1]. In Akap1-knockout (KO) mice with diabetes-induced cardiomyopathy, Akap1 deficiency inhibited complex I activity by preventing NDUFS1 translocation to mitochondria, exacerbating mitochondrial dysfunction and apoptosis, while restoration of AKAP1 promoted NDUFS1 translocation and alleviated diabetic cardiomyopathy [3]. In a pressure-overload-induced myocardial hypertrophy mouse model, Ndufs1 expression was downregulated in hypertrophic heart tissue, and Ndufs1 knockdown in cardiomyocytes led to mitochondrial dysfunction, while overexpression attenuated Ang II-mediated effects [6]. In hepatocellular carcinoma, agrimol B downregulated Ndufs1 through caspase 3-mediated degradation, promoting mitochondrial ROS accumulation and autophagy arrest [5]. In gastric cancer, downregulation of Ndufs1 promoted cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway [4].

In conclusion, Ndufs1 is essential for maintaining mitochondrial function and normal energy metabolism through its role in mitochondrial complex I. Studies using KO or overexpression mouse models have revealed its significance in multiple disease conditions such as heart failure, diabetes-related cardiomyopathy, and various cancers. Understanding the function of Ndufs1 provides potential therapeutic strategies for these diseases by targeting its associated pathways.