Overexpression of NDUFV1 alleviates renal damage by improving mitochondrial function in unilateral ureteral obstruction model mice

Abstract

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.

Explore the role of long noncoding RNAs and mRNAs in intracranial atherosclerotic stenosis: From the perspective of neutrophils

“…[ 50 ] Previous studies reported that NDUFV1 increases the activity of mitochondrial complex I. [ 47 ] In this study, NDUFV1 expression was upregulated in the ICAS group. Combined with the studies mentioned above, the increased NDUFV1 in neutrophils may promote the activity of mitochondrial complex I, increasing pro-inflammatory cytokine production and NF-κB activation and promoting the development of ICAS.…”

“…NDUFV1 is located on the mitochondrial complex I. [ 46 47 ] Clinically, mitochondrial complex I dysfunction is common in genetic diseases, especially human mitochondrial diseases. [ 48 ] Mitochondrial dysfunction is related to inflammation, oxidative stress, and cell apoptosis, and participates in the progression of atherosclerosis.…”

Expression Profiles of Kidney Mitochondrial Proteome during the Progression of the Unilateral Ureteral Obstruction: Focus on Energy Metabolism Adaptions

“…Based on the above, we consider our work’s perspective is useful in identification of proteins from the renal mitochondrial protein profiles which could be potential biomarkers of ON or therapeutic targets. In line with the latter, experimental results have shown that OXPHOS [ 53 , 54 , 55 ], inhibition of glycolysis [ 19 , 20 ], or enhancing FA metabolism [ 50 , 56 , 57 , 58 , 59 ] are potential therapeutic strategies related to the mitochondrial function that might decrease renal damage in the UUO.…”

Comprehensive analysis of lactate-related gene profiles and immune characteristics in lupus nephritis

“…NADH: Ubiquinone Oxidoreductase Core Subunit V1 (NDUFV1) is a nuclear-encoded structural subunit of CI and its mutations are associated with Leigh syndrome (LS), diffuse leukoencephalopathy, and Parkinson’s disease ( 48 , 49 ). According to previous research, the reinforcement expression of NDUFV1 has turned out to reduce serum creatinine and blood urea nitrogen, attenuate proximal tubule damage, and repress cell apoptosis in renal ischemia/reperfusion (I/R) mice, which may be due to the improved mitochondrial metabolism, and reduced oxidative stress by overexpressed NDUFV1 ( 50 , 51 ). Having shown that the expression level of NDUFV1 was decreased in LN in our study and the classical pathway analysis of IPA indicated that NDUFV1 was related to ‘oxidative phosphorylation’ and ‘mitochondrial dysfunction’, we thus speculate that NDUFV1 deficiency could impair mitochondrial metabolism and homeostasis in renal tissue, contributing to the progress of LN.…”