Ndufaf5-flox Mouse

Ndufaf5, also known as C20orf7, is a mitochondrial complex I (CI) assembly factor. It belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases and hydroxylates Arg-73 in the NDUFS7 subunit of human complex I at an early stage in the assembly pathway of complex I [2,4]. Complex I is crucial for mitochondrial respiratory chain function, and thus Ndufaf5 is of great biological importance in energy metabolism processes. The Dictyostelium model has been used to study Ndufaf5, where its disruption leads to CI deficiency, defects in growth and development, and an increase in autophagy [2].

Mutations in Ndufaf5 are linked to Leigh syndrome with phenotypic heterogeneity. Onset age shows a bimodal distribution. The early-onset group (age < 3 years) presents with psychomotor delay, seizure, respiratory failure, and hyponatremia, while the late-onset group (age ≥ 5 years) initially has normal development but then experiences slowly progressive dystonia [1]. Bilateral basal ganglia necrosis is a common radiological feature, with more brainstem and spinal cord involvement in early-onset patients. Additionally, prenatal manifestations such as brain cysts, corpus callosal malformations, non-immune hydrops fetalis, and growth restriction have been associated with biallelic Ndufaf5 variants [3].

In conclusion, Ndufaf5 is essential for the assembly of mitochondrial complex I, playing a crucial role in energy-related biological processes. Studies using models like Dictyostelium have revealed its function in growth, development, and autophagy. The discovery of its association with Leigh syndrome and prenatal abnormalities through genetic studies has enhanced our understanding of related disease mechanisms, providing insights for diagnosis and potential treatment strategies.