NDUFS7, the NADH dehydrogenase Fe-S protein 7, is a crucial subunit of respiratory chain complex I in mitochondria. Complex I is involved in oxidative phosphorylation, a key metabolic pathway for generating ATP, the energy currency of cells. Thus, NDUFS7 is essential for normal mitochondrial function and cellular energy production [4].

In a study of dogs with Leigh syndrome, a missense variant NDUFS7:c.535G > A or p.(Val179Met) was identified. Genotypes co-segregated with the phenotype in the investigated litter, consistent with autosomal recessive inheritance. In a Drosophila melanogaster model, overexpression of wild-type NDUFS7 partially rescued pupal lethality upon knockdown of the fly ortholog ND-20, while the mutant overexpression did not, indicating the pathogenicity of the identified variant [1]. In HEK293T cells, mutation of NDUFS7 led to reduced cell proliferation, elevated cell death, and increased oxidative stress susceptibility. The upregulation of SLC7A11 was crucial in mitigating cell death from NDUFS7 deficiency by enhancing cystine import and promoting reduced glutathione biosynthesis [3].

In pancreatic cancer, a first-in-class small-molecule NDUFS7 antagonist, DX2-201, inhibited oxidative phosphorylation, suppressing cell line proliferation. A resistant clone had a pV91M mutation in NDUFS7, indicating its drug-binding site [2]. In skin cutaneous melanoma, NDUFS7 was a hub gene in the protein-protein interaction network. siRNA knockdown of NDUFS7 decreased the activity, proliferation, and migration of A375 and WM115 cell lines [5].

In conclusion, NDUFS7 is vital for mitochondrial function and energy production through its role in complex I. Studies in different models, such as Drosophila and cell lines, have revealed its significance in diseases like Leigh syndrome, pancreatic cancer, and cutaneous melanoma. Understanding NDUFS7 provides insights into the mechanisms of these diseases and potential therapeutic strategies targeting mitochondrial function.