Department of Nephrology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Cell Biol Int. 2022 Mar;46(3):381-390. doi: 10.1002/cbin.11736. Epub 2022 Jan 3.
Mitochondrial homeostasis plays essential role for the proper functioning of the kidney. NADH-ubiquinone oxidoreductase core subunit V1 (NDUFV1) is an enzyme in the complex I of electron transport chain (ETC) in mitochondria. In the present study, we examined the effects of NDUFV1 on renal function in unilateral ureteral obstruction (UUO) model mice. Our data showed that increased expression of NDUFV1 improves kidney function as evidenced by the decreases in blood urea nitrogen and serum creatinine in UUO mice. Moreover, NDUFV1 also maintains renal structures and alleviates renal fibrosis induced by UUO surgery. Mechanistically, NDUFV1 mitigates the increased oxidative stress in the kidney in UUO model mice. Meanwhile, increased expression of NDUFV1 in the kidney improves the integrity of the complex I and potentiates the complex I activity. Overall, these results indicate that the ETC complex I plays a beneficial role against renal dysfunction induced by acute kidney injury such as UUO. Therefore, NDUFV1 might be a druggable target for developing agents for dealing with disabled mitochondria-associated renal diseases.
线粒体动态平衡对于肾脏的正常功能至关重要。NADH-泛醌氧化还原酶核心亚基 V1（NDUFV1）是线粒体电子传递链（ETC）复合物 I 中的一种酶。在本研究中，我们研究了 NDUFV1 在单侧输尿管梗阻（UUO）模型小鼠中对肾功能的影响。我们的数据表明，NDUFV1 的表达增加可改善肾功能，表现为 UUO 小鼠的血尿素氮和血清肌酐降低。此外，NDUFV1 还可维持肾脏结构并减轻 UUO 手术引起的肾纤维化。从机制上讲，NDUFV1 减轻了 UUO 模型小鼠肾脏中氧化应激的增加。同时，肾脏中 NDUFV1 的表达增加可提高复合物 I 的完整性并增强复合物 I 的活性。总的来说，这些结果表明 ETC 复合物 I 在对抗 UUO 等急性肾损伤引起的肾功能障碍方面具有有益作用。因此，NDUFV1 可能是开发针对与受损线粒体相关的肾脏疾病的药物的一个有前途的靶点。
