“NDUFS4”的意思、由来-开放百科全书

Function

Complex I, or NADH:ubiquinone oxidoreductase, the first multisubunit enzyme complex of the mitochondrial respiratory chain, plays a vital role in cellular ATP production, the primary source of energy for many crucial processes in living cells. It removes electrons from NADH and passes them by a series of different protein-coupled redox centers to the electron acceptor ubiquinone. In well-coupled mitochondria, the electron flux leads to ATP generation via the building of a proton gradient across the inner membrane. Complex I is composed of at least 41 subunits, of which 7 are encoded by the mitochondrial genome (ND1-6, ND4L) and the remainder by nuclear genes.^[1]^[3]

Clinical significance

Mutations in the NDUFS4 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.^[9]^[10] 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.^[11] However, the majority of cases are caused by mutations in nuclear-encoded genes.^[12]^[13] 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.^[14] Complex I deficiency with autosomal recessive inheritance results from mutation in nuclear-encoded subunit genes, including NDUFV1, NDUFV2, NDUFS1, NDUFS2, NDUFS3, NDUFS6, NDUFS7, NDUFS8, NDUFA2, NDUFA11, NDUFAF3, NDUFAF10, NDUFB3, NDUFB9, ACAD9, FOXRED1, and MTFMT.

Interactions

NDUFS4 has been shown to have 58 binary protein-protein interactions including 57 co-complex interactions. NDUFS4 appears to interact with UBE2G2.^[15]

References

1. ^¹{{cite journal | vauthors = van den Heuvel L, Ruitenbeek W, Smeets R, Gelman-Kohan Z, Elpeleg O, Loeffen J, Trijbels F, Mariman E, de Bruijn D, Smeitink J | title = Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit | journal = American Journal of Human Genetics | volume = 62 | issue = 2 | pages = 262–8 | date = February 1998 | pmid = 9463323 | pmc = 1376892 | doi = 10.1086/301716 }}
2. ^{{cite journal | vauthors = Emahazion T, Beskow A, Gyllensten U, Brookes AJ | title = Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain | journal = Cytogenetics and Cell Genetics | volume = 82 | issue = 1–2 | pages = 115–9 | date = Nov 1998 | pmid = 9763677 | pmc = | doi = 10.1159/000015082 }}
3. ^¹²{{cite web | title = Entrez Gene: NDUFS4 NADH dehydrogenase (ubiquinone) Fe-S protein 4, 18kDa (NADH-coenzyme Q reductase)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4724| access-date = }}{{PD-notice}}
4. ^{{cite web|url=https://www.ncbi.nlm.nih.gov/gene/65260|title=Entrez Gene: Cytochrome c oxidase assembly factor 7 (putative)|access-date=2018-08-08}}{{PD-notice}}
5. ^{{Cite web|url=https://amino.heartproteome.org/web/protein/O43181|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel|website=amino.heartproteome.org|access-date=2018-08-28}}
6. ^{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
7. ^{{Cite web|url=https://www.uniprot.org/uniprot/O43181|title=NDUFS4 - NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial precursor - Homo sapiens (Human) - NDUFS4 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-28}}{{CC-notice|cc=by4}}
8. ^{{cite journal | vauthors = | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158–D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}
9. ^{{cite journal | vauthors = Kirby DM, Salemi R, Sugiana C, Ohtake A, Parry L, Bell KM, Kirk EP, Boneh A, Taylor RW, Dahl HH, Ryan MT, Thorburn DR | title = NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency | journal = The Journal of Clinical Investigation | volume = 114 | issue = 6 | pages = 837–45 | date = September 2004 | pmid = 15372108 | pmc = 516258 | doi = 10.1172/JCI20683 }}
10. ^{{cite journal | vauthors = McFarland R, Kirby DM, Fowler KJ, Ohtake A, Ryan MT, Amor DJ, Fletcher JM, Dixon JW, Collins FA, Turnbull DM, Taylor RW, Thorburn DR | title = De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency | journal = Annals of Neurology | volume = 55 | issue = 1 | pages = 58–64 | date = January 2004 | pmid = 14705112 | doi = 10.1002/ana.10787 }}
11. ^{{cite journal | vauthors = Haack TB, Haberberger B, Frisch EM, Wieland T, Iuso A, Gorza M, Strecker V, Graf E, Mayr JA, Herberg U, Hennermann JB, Klopstock T, Kuhn KA, Ahting U, Sperl W, Wilichowski E, Hoffmann GF, Tesarova M, Hansikova H, Zeman J, Plecko B, Zeviani M, Wittig I, Strom TM, Schuelke M, Freisinger P, Meitinger T, Prokisch H | title = Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing | journal = Journal of Medical Genetics | volume = 49 | issue = 4 | pages = 277–83 | date = April 2012 | pmid = 22499348 | doi = 10.1136/jmedgenet-2012-100846 }}
12. ^{{cite journal | vauthors = Loeffen JL, Smeitink JA, Trijbels JM, Janssen AJ, Triepels RH, Sengers RC, van den Heuvel LP | title = Isolated complex I deficiency in children: clinical, biochemical and genetic aspects | journal = Human Mutation | volume = 15 | issue = 2 | pages = 123–34 | date = 2000 | pmid = 10649489 | doi = 10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P }}
13. ^{{cite journal | vauthors = Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA | title = Respiratory chain complex I deficiency | journal = American Journal of Medical Genetics | volume = 106 | issue = 1 | pages = 37–45 | date = 2001 | pmid = 11579423 | doi = 10.1002/ajmg.1397 }}
14. ^{{cite journal | vauthors = Robinson BH | title = Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect | journal = Biochimica et Biophysica Acta | volume = 1364 | issue = 2 | pages = 271–86 | date = May 1998 | pmid = 9593934 | doi = 10.1016/s0005-2728(98)00033-4 }}
15. ^{{cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFS4 | title = 58 binary interactions found for search term NDUFS4 | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-28 }}

Further reading

{{cite journal | vauthors = Leshinsky-Silver E, Lebre AS, Minai L, Saada A, Steffann J, Cohen S, Rötig A, Munnich A, Lev D, Lerman-Sagie T | title = NDUFS4 mutations cause Leigh syndrome with predominant brainstem involvement | journal = Molecular Genetics and Metabolism | volume = 97 | issue = 3 | pages = 185–9 | date = July 2009 | pmid = 19364667 | doi = 10.1016/j.ymgme.2009.03.002 }}

{{cite journal | vauthors = Papa S, Sardanelli AM, Scacco S, Petruzzella V, Technikova-Dobrova Z, Vergari R, Signorile A | title = The NADH: ubiquinone oxidoreductase (complex I) of the mammalian respiratory chain and the cAMP cascade | journal = Journal of Bioenergetics and Biomembranes | volume = 34 | issue = 1 | pages = 1–10 | date = February 2002 | pmid = 11860175 | doi = 10.1023/A:1013863018115 }}

{{cite journal | vauthors = Pilkington SJ, Skehel JM, Gennis RB, Walker JE | title = Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NAD-reducing hydrogenase | journal = Biochemistry | volume = 30 | issue = 8 | pages = 2166–75 | date = February 1991 | pmid = 1900194 | doi = 10.1021/bi00222a021 }}

{{cite journal | vauthors = Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA | title = cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed | journal = Biochemical and Biophysical Research Communications | volume = 253 | issue = 2 | pages = 415–22 | date = December 1998 | pmid = 9878551 | doi = 10.1006/bbrc.1998.9786 }}

{{cite journal | vauthors = Triepels RH, Hanson BJ, van den Heuvel LP, Sundell L, Marusich MF, Smeitink JA, Capaldi RA | title = Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns | journal = The Journal of Biological Chemistry | volume = 276 | issue = 12 | pages = 8892–7 | date = March 2001 | pmid = 11112787 | doi = 10.1074/jbc.M009903200 }}

{{cite journal | vauthors = Papa S, Scacco S, Sardanelli AM, Vergari R, Papa F, Budde S, van den Heuvel L, Smeitink J | title = Mutation in the NDUFS4 gene of complex I abolishes cAMP-dependent activation of the complex in a child with fatal neurological syndrome | journal = FEBS Letters | volume = 489 | issue = 2–3 | pages = 259–62 | date = February 2001 | pmid = 11165261 | doi = 10.1016/S0014-5793(00)02334-6 }}

{{cite journal | vauthors = Petruzzella V, Vergari R, Puzziferri I, Boffoli D, Lamantea E, Zeviani M, Papa S | title = A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome | journal = Human Molecular Genetics | volume = 10 | issue = 5 | pages = 529–35 | date = March 2001 | pmid = 11181577 | doi = 10.1093/hmg/10.5.529 }}

{{cite journal | vauthors = Roef MJ, Reijngoud DJ, Jeneson JA, Berger R, de Meer K | title = Resting oxygen consumption and in vivo ADP are increased in myopathy due to complex I deficiency | journal = Neurology | volume = 58 | issue = 7 | pages = 1088–93 | date = April 2002 | pmid = 11940698 | doi = 10.1212/wnl.58.7.1088 }}

{{cite journal | vauthors = Lee BH, Lee H, Xiong L, Zhu JK | title = A mitochondrial complex I defect impairs cold-regulated nuclear gene expression | journal = The Plant Cell | volume = 14 | issue = 6 | pages = 1235–51 | date = June 2002 | pmid = 12084824 | pmc = 150777 | doi = 10.1105/tpc.010433 }}

{{cite journal | vauthors = Papa S | title = The NDUFS4 nuclear gene of complex I of mitochondria and the cAMP cascade | journal = Biochimica et Biophysica Acta | volume = 1555 | issue = 1–3 | pages = 147–53 | date = September 2002 | pmid = 12206907 | doi = 10.1016/S0005-2728(02)00270-0 }}

{{cite journal | vauthors = Bénit P, Steffann J, Lebon S, Chretien D, Kadhom N, de Lonlay P, Goldenberg A, Dumez Y, Dommergues M, Rustin P, Munnich A, Rötig A | title = Genotyping microsatellite DNA markers at putative disease loci in inbred/multiplex families with respiratory chain complex I deficiency allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the NDUFS4 gene in Leigh syndrome | journal = Human Genetics | volume = 112 | issue = 5–6 | pages = 563–6 | date = May 2003 | pmid = 12616398 | doi = 10.1007/s00439-002-0884-2 }}

{{cite journal | vauthors = Scacco S, Petruzzella V, Budde S, Vergari R, Tamborra R, Panelli D, van den Heuvel LP, Smeitink JA, Papa S | title = Pathological mutations of the human NDUFS4 gene of the 18-kDa (AQDQ) subunit of complex I affect the expression of the protein and the assembly and function of the complex | journal = The Journal of Biological Chemistry | volume = 278 | issue = 45 | pages = 44161–7 | date = November 2003 | pmid = 12944388 | doi = 10.1074/jbc.M307615200 }}

{{cite journal | vauthors = Budde SM, van den Heuvel LP, Smeets RJ, Skladal D, Mayr JA, Boelen C, Petruzzella V, Papa S, Smeitink JA | title = Clinical heterogeneity in patients with mutations in the NDUFS4 gene of mitochondrial complex I | journal = Journal of Inherited Metabolic Disease | volume = 26 | issue = 8 | pages = 813–5 | year = 2004 | pmid = 14765537 | doi = 10.1023/B:BOLI.0000010003.14113.af }}

{{cite journal | vauthors = Papa S, Petruzzella V, Scacco S, Vergari R, Panelli D, Tamborra R, Corsi P, Picciariello M, Lambo R, Bertini E, Santorelli FM | title = Respiratory complex I in brain development and genetic disease | journal = Neurochemical Research | volume = 29 | issue = 3 | pages = 547–60 | date = March 2004 | pmid = 15038602 | doi = 10.1023/B:NERE.0000014825.42365.16 }}

{{cite journal | vauthors = Petruzzella V, Panelli D, Torraco A, Stella A, Papa S | title = Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of the splice variants | journal = FEBS Letters | volume = 579 | issue = 17 | pages = 3770–6 | date = July 2005 | pmid = 15975579 | doi = 10.1016/j.febslet.2005.05.035 }}

{{cite journal | vauthors = Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R | title = Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry | journal = Nature Methods | volume = 2 | issue = 8 | pages = 591–8 | date = August 2005 | pmid = 16094384 | doi = 10.1038/nmeth776 }}

1 : Human proteins

Structure

Function

Clinical significance

Interactions

References

Further reading