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NADH dehydrogenase, subunit 5 (complex I)
Symbols ND5 ; MTND5
External IDs OMIM516005 HomoloGene36212 GeneCards: ND5 Gene
Species Human Mouse
Entrez 4540 17721
Ensembl ENSG00000198786 ENSMUSG00000064367
UniProt P03915 None
RefSeq (mRNA) None None
RefSeq (protein) n/a NP_904338
Location (UCSC) Chr MT:
0.01 – 0.01 Mb
Chr MT:
0.01 – 0.01 Mb
PubMed search [1] [2]

NADH-ubiquinone oxidoreductase chain 5 is a protein that in humans is encoded by the mitochondrial gene MT-ND5.[1] The ND5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[2] Variations in MT-ND5 are associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) as well as some symptoms of Leigh's syndrome and Leber's hereditary optic neuropathy (LHON).[3][4]


MT-ND5 is located in mitochondrial DNA from base pair 12,337 to 14,148.[1] The MT-ND5 gene produces a 67 kDa protein composed of 603 amino acids.[5][6] MT-ND5 is one of seven mitochondrially-encoded subunits of the enzyme NADH dehydrogenase (ubiquinone). Also known as Complex I, it is the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centres and the NADH binding site. MT-ND5 and the rest of the mitochondrially encoded subunits are the most hydrophobic of the subunits of Complex I and form the core of the transmembrane region.[2]


MT-ND5 is a subunit of the respiratory chain Complex I that is believed to belong to the minimal assembly of core proteins required to catalyze NADH dehydrogenation and electron transfer to ubiquinone (coenzyme Q10).[7] Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[2]

Clinical Significance[edit]

A small percentage of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) are caused by a G>A mutation at base pair 13513 in the MT-ND5 gene. Mutations in the MT-ND5 gene cause impaired Complex I function of the mitochondrial electron transport system, impairing those tissues that require significant energy input, such as the brain and muscles. Those with MT-ND5 mutations can display the major features of MELAS in some patients, as well as symptoms of Leigh's syndrome and/or Leber's hereditary optic neuropathy (LHON) in others.[3][4]


MT-ND5 interacts with Glutamine synthetase (GLUL), LIG4 and YME1L1.[1]


  1. ^ a b c "Entrez Gene: MT-ND5 NADH dehydrogenase subunit 5". 
  2. ^ a b c Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed. ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847. 
  3. ^ a b DiMauro, S; Hirano, M; Pagon, RA; Adam, MP; Ardinger, HH; Bird, TD; Dolan, CR; Fong, CT; Smith, RJH; Stephens, K (1993). "MELAS". GeneReviews. PMID 20301411. 
  4. ^ a b "MT-ND5". Genetics Home Reference. US National Library of Medicine. Retrieved 23 March 2015. 
  5. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS et al. (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338. 
  6. ^ "NADH-ubiquinone oxidoreductase chain 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). 
  7. ^ "MT-ND5 - NADH-ubiquinone oxidoreductase chain 5 - Homo sapiens (Human)". a hub for protein information. The UniProt Consortium. 

External links[edit]

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