Biology:NDUFS6
 Generic protein structure example |
NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial is an enzyme that in humans is encoded by the NDUFS6 gene.[1][2]
Function
The multisubunit NADH:ubiquinone oxidoreductase (complex I) is the first enzyme complex in the electron transport chain of mitochondria. The iron-sulfur protein (IP) fraction is made up of 7 subunits, including NDUFS6.[2]
Clinical significance
Mutations in the NDUFS6 gene are associated with mitochondrial Complex I deficiency, and are inherited in an autosomal recessive manner. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders.[3][4] 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.[5] However, the majority of cases are caused by mutations in nuclear-encoded genes.[6][7] 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.[8]
In NDUFS6 mutations the presentation is typically a neonatal lactic acidosis that is swiftly fatal, coupled with multi-system failure.[3][5][8]
See also
References
- ↑ "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenetics and Cell Genetics 82 (1–2): 115–9. Nov 1998. doi:10.1159/000015082. PMID 9763677.
- ↑ 2.0 2.1 "Entrez Gene: NDUFS6 NADH dehydrogenase (ubiquinone) Fe-S protein 6, 13kDa (NADH-coenzyme Q reductase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4726.
- ↑ 3.0 3.1 "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–45. Sep 2004. doi:10.1172/JCI20683. PMID 15372108.
- ↑ "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology 55 (1): 58–64. Jan 2004. doi:10.1002/ana.10787. PMID 14705112.
- ↑ 5.0 5.1 "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–83. Apr 2012. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. https://epub.ub.uni-muenchen.de/21895/1/oa_21895.pdf.
- ↑ "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation 15 (2): 123–34. 2000. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489.
- ↑ "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. 2001. doi:10.1002/ajmg.1397. PMID 11579423.
- ↑ 8.0 8.1 "Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1364 (2): 271–86. May 1998. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.
Further reading
- "cDNA sequence and chromosomal localization of the remaining three human nuclear encoded iron sulphur protein (IP) subunits of complex I: the human IP fraction is completed". Biochemical and Biophysical Research Communications 247 (3): 751–8. Jun 1998. doi:10.1006/bbrc.1998.8882. PMID 9647766.
- "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochemical and Biophysical Research Communications 253 (2): 415–22. Dec 1998. doi:10.1006/bbrc.1998.9786. PMID 9878551.
- "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology 22 (6): 707–16. Jun 2004. doi:10.1038/nbt971. PMID 15146197.
- "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–45. Sep 2004. doi:10.1172/JCI20683. PMID 15372108.
- "Transcriptome analysis of human gastric cancer". Mammalian Genome 16 (12): 942–54. Dec 2005. doi:10.1007/s00335-005-0075-2. PMID 16341674.
- "Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I". Molecular and Cellular Biology 27 (12): 4228–37. Jun 2007. doi:10.1128/MCB.00074-07. PMID 17438127.
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