NDUFS2

NDUFS2 is located on the q arm of chromosome 1 in position 23.3 and has 15 exons.[7] The NDUFS2 gene produces a 52.5 kDa protein composed of 463 amino acids.[8][9] NDUFS2, the protein encoded by this gene, is a member of the complex I 49 kDa subunit family. It is a peripheral membrane protein on the matrix side of the inner mitochondrial membrane. It contains a cofactor binding site for a [4Fe-4S] cluster, a transit peptide, 5 turns, 11 beta strands, and 18 alpha helixes.[10][11] Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[7]

Mitochondrial complex I is the first multimeric complex of the respiratory chain that catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mammalian mitochondrial complex I is an assembly of at least 43 different subunits. Seven of the subunits are encoded by the mitochondrial genome; the remainder are the products of nuclear genes. The iron-sulfur protein (IP) fraction of complex I is made up of 7 subunits, including NDUFS2.[7] Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to the stabilization of the early intermediate complex.[12][13][10][11]

Mutations in the NDUFS2 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders.[14][15] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype–phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible.[16] However, the majority of cases are caused by mutations in nuclear-encoded genes.[17][18] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[19]

NDUFS2 has been shown to have 121 binary protein-protein interactions including 112 co-complex interactions. NDUFS2 appears to interact with NDUFS3, MKLN1, EGR2, HMOX2, CENPU, and TNFRSF14.[20]

• NDUFS1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.