NDUFS3

NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial is an is_associated_with::enzyme that in humans is encoded by the NDUFS3 is_associated_with::gene.

Function
The multisubunit NADH:ubiquinone oxidoreductase (complex I) is the first enzyme complex in the is_associated_with::electron transport chain of mitochondria. The is_associated_with::iron-sulfur protein (IP) fraction of complex I is made up of 7 subunits.

Clinical significance
Mutations in the NDUFS3 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. 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. However, the majority of cases are caused by mutations in nuclear-encoded genes. 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.

Model organisms
is_associated_with::Model organisms have been used in the study of NDUFS3 function. A conditional is_associated_with::knockout mouse line, called Ndufs3tm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on is_associated_with::mutant mice and six significant abnormalities were observed. No is_associated_with::homozygous is_associated_with::mutant embryos were identified during gestation, and therefore none survived until is_associated_with::weaning. The remaining tests were carried out on is_associated_with::heterozygous mutant adult mice; males had an increased lean body mass and heart weight, and a decrease in some is_associated_with::plasma chemistry and is_associated_with::haematology parameters.