NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial

Function

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for catalysing the entry and efficient transfer of electrons within complex I. Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes.

Classification

Family (Pfam)

PF13510 Fer2_4, PF22151 Fer4_NDSU1, PF22117 Fer4_Nqo3, PF00384 Molybdopterin, PF10588 NADH-G_4Fe-4S_3, PF09326 NADH_dhqG_C

InterPro

2Fe-2S_ferredoxin-like_sf, 2Fe-2S_ferredoxin-type, Mopterin_OxRdtase, Mopterin_OxRdtase_4Fe-4S_dom, NADH_UbQ_OxRdtase_75kDa_su_CS, NADH_UbQ_OxRdtase_ferredoxin, NADH_UbQ_OxRdtase_Gsu, NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd, NDUFS1-like_C, Prok_molybdopt-oxidoreductase

Functional cluster

Oxidoreductases, Catalases & Peroxidases

Experimental structures · PDB · 7

• 5XTB EM 3.40A
• 5XTD EM 3.70A
• 5XTH EM 3.90A
• 5XTI EM 17.40A
• 9CWT EM 3.44A
• 9I4I EM 2.63A
• 9TI4 EM 2.66A

A predicted model is available from AlphaFold.

Gene Ontology · 16

• GO:0005743 mitochondrial inner membrane
• GO:0005758 mitochondrial intermembrane space
• GO:0005759 mitochondrial matrix
• GO:0005739 mitochondrion
• GO:0045271 respiratory chain complex I
• GO:0051537 2 iron, 2 sulfur cluster binding
• GO:0051539 4 iron, 4 sulfur cluster binding
• GO:0009055 electron transfer activity
• GO:0046872 metal ion binding
• GO:0008137 NADH dehydrogenase (ubiquinone) activity
• GO:0016651 oxidoreductase activity, acting on NAD(P)H
• GO:0009060 aerobic respiration
• GO:0045333 cellular respiration
• GO:0006120 mitochondrial electron transport, NADH to ubiquinone
• GO:0032981 mitochondrial respiratory chain complex I assembly
• GO:0042776 proton motive force-driven mitochondrial ATP synthesis

Disease associations

• mitochondrial complex I deficiency, nuclear type 5 MONDO:0032610

Drugs targeting this protein · 2

• METFORMIN HYDROCHLORIDE inhibitor
• ME-344 inhibitor

Related proteins · sequence + function similarity

• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 1.00
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 1.00
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 1.00
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 1.00
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 1.00
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 0.99
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 0.99
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 1, mitochondrial 0.88
• NADH dehydrogenase [ubiquinone] iron-sulfur protein 1, mitochondrial 0.84
• NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial 0.84
• NADH-ubiquinone oxidoreductase 78 kDa subunit, mitochondrial 0.80
• NADH-ubiquinone oxidoreductase 78 kDa subunit, mitochondrial 0.78

Co-cited proteins · studied together in the literature

• NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial 1 shared papers
• Phenylalanine--tRNA ligase, mitochondrial 1 shared papers
• Elongation factor Ts, mitochondrial 1 shared papers
• E3 ubiquitin-protein ligase Mdm2 1 shared papers
• E3 ubiquitin-protein ligase Mdm2 1 shared papers

Literature · 12 cited papers

• Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer. Cells · 2019
• MDM2 Integrates Cellular Respiration and Apoptotic Signaling through NDUFS1 and the Mitochondrial Network. Mol. Cell · 2019
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. J. Med. Genet. · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J. Biol. Chem. · 2003
• Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency. Am. J. Hum. Genet. · 2001
• Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase. Eur. J. Biochem. · 1991