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 of mitochondria, which is crucial for energy metabolism, generating ATP through oxidative phosphorylation. Maintaining mitochondrial function is essential for the normal operation of cells and organisms [2,3].

Pathogenic variants in NDUFV1 disrupt mitochondrial complex I. In children, this leads to neuroregression with leukoencephalopathy and basal ganglia involvement. MRI patterns in such patients are classified into Leigh, mitochondrial leukodystrophy, and mixed types. Comorbidities like hypertonia, ocular abnormalities, feeding issues, and hypotonia are common at onset. The c.1156C>T variant in exon 8 is prevalent among Asians and is associated with irritability and dystonia. Higher mortality is seen in children with Leigh-type MRI pattern and those not receiving mitochondrial cocktail [1]. In mouse models, reduced NDUFV1 in renal ischemia/reperfusion mice leads to kidney dysfunction, while increased expression alleviates detrimental outcomes. Also, in unilateral ureteral obstruction model mice, increased NDUFV1 improves kidney function, maintains renal structures, and alleviates renal fibrosis [2,3].

In conclusion, NDUFV1 plays a vital role in maintaining mitochondrial function, especially in energy metabolism through its role in mitochondrial complex I. Research using mouse models has revealed its significance in preventing renal dysfunction and has provided insights into the pathogenesis of NDUFV1-related mitochondrial complex-1 disorders in children, emphasizing its potential as a therapeutic target for related diseases.