NDUFS3, or NADH dehydrogenase [ubiquinone] ferrithionein 3, is a non-catalytic core subunit of mitochondrial respiratory chain complex I. Complex I is crucial for cellular energy production, and thus NDUFS3 plays an essential role in the energy metabolism of cells. It is associated with various biological processes such as oxidative phosphorylation, which is vital for generating ATP [3,4,5].

In a sepsis-induced acute kidney injury (SI-AKI) rat model, overexpression of NDUFS3 inhibited LPS-induced ferroptosis and mitochondrial damage in HK-2 cells through the AMPK pathway, suggesting its protective role in SI-AKI [1]. In PINK1B9 transgenic Drosophila, down-regulation of NDUFS3 gene expression may have a protective effect, potentially related to reducing oxidative stress and restoring mitochondrial function [7]. In addition, NDUFS3 is underexpressed in atherosclerosis and chronic stress, and lower levels are associated with a worse prognosis [2]. It is also downregulated in atherosclerosis and venous thrombosis, and may serve as a potential biomarker for these diseases [6]. In serous ovarian adenocarcinoma, reduced NDUFS3 expression is correlated with advanced stage, suboptimal residual disease, and shorter survival, suggesting its contribution to the development of this cancer [8].

In conclusion, NDUFS3 is essential for mitochondrial function and energy metabolism. Research using animal models, like the SI-AKI rat model and PINK1B9 transgenic Drosophila, has revealed its roles in various disease conditions including SI-AKI, Parkinson's disease-related models, atherosclerosis, venous thrombosis, and serous ovarian cancer. These findings provide potential therapeutic targets for these diseases by highlighting the importance of NDUFS3-related pathways [1,2,6,7,8].

References:

1. Wang, YuChen, Lv, WuYang, Ma, XiaoTong, Yin, MengJiao, Jin, YingYu. 2024. NDUFS3 alleviates oxidative stress and ferroptosis in sepsis induced acute kidney injury through AMPK pathway. In International immunopharmacology, 143, 113393. doi:10.1016/j.intimp.2024.113393. https://pubmed.ncbi.nlm.nih.gov/39426231/

2. Yang, Yin, Li, Jing-Hui, Yao, Bo-Chen, Wang, Lian-Qun, Guo, Zhi-Gang. 2023. NDUFB11 and NDUFS3 play a role in atherosclerosis and chronic stress. In Aging, 15, 8026-8043. doi:10.18632/aging.204947. https://pubmed.ncbi.nlm.nih.gov/37642954/

3. D'Angelo, Luigi, Astro, Elisa, De Luise, Monica, Fernandez-Vizarra, Erika, Iommarini, Luisa. . NDUFS3 depletion permits complex I maturation and reveals TMEM126A/OPA7 as an assembly factor binding the ND4-module intermediate. In Cell reports, 35, 109002. doi:10.1016/j.celrep.2021.109002. https://pubmed.ncbi.nlm.nih.gov/33882309/

4. Samanta, Debopam, Veerapandiyan, Aravindhan, Burrow, Thomas A, Gokden, Murat. 2021. Mitochondrial Ultrastructural Defects in NDUFS3-Related Disorder. In Journal of pediatric neurosciences, 16, 299-302. doi:10.4103/jpn.JPN_182_20. https://pubmed.ncbi.nlm.nih.gov/36531773/

5. Yuan, Ningyang, Shen, Lei, Peng, Qian, You, Xue, Feng, Ying. 2024. SRSF1 Is Required for Mitochondrial Homeostasis and Thermogenic Function in Brown Adipocytes Through its Control of Ndufs3 Splicing. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2306871. doi:10.1002/advs.202306871. https://pubmed.ncbi.nlm.nih.gov/38569495/

6. Ma, Yan-Hong, Yang, Yin, Li, Jing-Hui, Guo, Zhi-Gang, Guo, Su-Zhi. . NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: Potential markers of atherosclerosis and venous thrombosis. In Medicine, 102, e36133. doi:10.1097/MD.0000000000036133. https://pubmed.ncbi.nlm.nih.gov/37986300/

7. Fan, Xueting, Tang, Yafang, Wei, Zaiwa, Cui, Yilei, Li, Qinghua. 2024. Mitochondrial dysfunction and NDUFS3: Insights from a PINK1B9 Drosophila model in Parkinson's disease pathogenesis. In Neuroscience letters, 839, 137917. doi:10.1016/j.neulet.2024.137917. https://pubmed.ncbi.nlm.nih.gov/39102941/

8. Wang, Pei, Cheng, Xiaodong, Fu, Zhiqin, Lu, Weiguo, Xie, Xing. . Reduced expression of NDUFS3 and its clinical significance in serous ovarian cancer. In International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 23, 622-9. doi:10.1097/IGC.0b013e318287a90d. https://pubmed.ncbi.nlm.nih.gov/23446378/