Ndufv1, short for NADH: ubiquinone oxidoreductase core subunit V1, is an important subunit of mitochondrial complex I. Mitochondrial complex I is a key component in the electron transport chain, which is crucial for oxidative phosphorylation, the process that generates adenosine triphosphate (ATP), the energy currency of the cell. Thus, Ndufv1 is of great significance in maintaining normal mitochondrial function and energy metabolism [2,3].

Pathogenic variants in the Ndufv1 gene disrupt mitochondrial complex I, leading to various disorders. In a retrospective case series, children with Ndufv1-related disorders showed comorbidities like hypertonia, ocular abnormalities, feeding issues, and hypotonia at onset. MRI patterns in these patients were classified into three types: Leigh, mitochondrial leukodystrophy, and mixed. Different phenotypes were associated with specific symptoms, such as breathing difficulties in Leigh-type and dystonia in mixed phenotypes. The c.1156C>T variant in exon 8 was common among Asians and related to irritability and dystonia [1]. In mouse models, reduced Ndufv1 in kidneys of renal ischemia/reperfusion mice led to kidney dysfunction, while increased expression attenuated detrimental outcomes. Also, in the unilateral ureteral obstruction model mice, overexpression of Ndufv1 improved kidney function, maintained renal structures, and alleviated renal fibrosis [2,3].

In conclusion, Ndufv1 plays a vital role in maintaining mitochondrial homeostasis, especially in energy metabolism. Studies on Ndufv1, including those using mouse models, have revealed its significance in mitochondrial-related disorders such as mitochondrial complex-1 disorders and renal diseases associated with mitochondrial dysfunction. Understanding Ndufv1 can potentially provide new therapeutic strategies for these diseases.