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AliasesND2, complex I ND2 subunit, NAD2, NADH-ubiquinone oxidoreductase chain 2, MT-MTND2
External IDsMGI: 102500 HomoloGene: 5019 GeneCards: ND2
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)n/aChr M: 0 – 0 Mb
PubMed search[2][3]
View/Edit HumanView/Edit Mouse
Location of the MT-ND2 gene in the human mitochondrial genome. MT-ND2 is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).

Mitochondrially encoded NADH dehydrogenase 2 is protein that in humans is encoded by the mitochondrial gene MT-ND2 gene.[4] The ND2 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.[5] Variants of MT-ND2 are associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Leigh's syndrome (LS), Leber's hereditary optic neuropathy (LHON) and increases in adult BMI.[6][7][8]


MT-ND2 is located in mitochondrial DNA from base pair 4,470 to 5,511.[4] The MT-ND2 gene produces a 39 kDa protein composed of 347 amino acids.[9][10] MT-ND2 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-ND2 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.[5]


MT-ND2 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).[11] 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.[5]

Clinical significance[edit]

Pathogenic variants of the mitochondrial gene MT-ND2 are known to cause mtDNA-associated Leigh syndrome, as are variants of MT-ATP6, MT-TL1, MT-TK, MT-TW, MT-TV, MT-ND1, MT-ND3, MT-ND4, MT-ND5, MT-ND6 and MT-CO3. Abnormalities in mitochondrial energy generation result in neurodegenerative disorders like Leigh syndrome, which is characterized by an onset of symptoms between 12 months and three years of age. The symptoms frequently present themselves following a viral infection and include movement disorders and peripheral neuropathy, as well as hypotonia, spasticity and cerebellar ataxia. Roughly half of affected patients die of respiratory or cardiac failure by the age of three. Leigh syndrome is a maternally inherited disorder and its diagnosis is established through genetic testing of the aforementioned mitochondrial genes, including MT-ND2.[6] These complex I genes have been associated with a variety of neurodegenerative disorders, including Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and the previously mentioned Leigh syndrome.[7]

Mitochondrial dysfunction resulting from variants of MT-ND2, MT-ND1 and MT-ND4L have been linked to BMI in adults and implicated in metabolic disorders including obesity, diabetes and hypertension.[8]


  1. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064345 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:".
  3. ^ "Mouse PubMed Reference:".
  4. ^ a b "Entrez Gene: MT-ND2 NADH dehydrogenase subunit 2".
  5. ^ a b c Voet DJ, Voet JG, Pratt CW (2013). "Chapter 18: Mitochondrial ATP synthesis". Fundamentals of Biochemistry (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 978-0-47054784-7.
  6. ^ a b Thorburn DR, Rahman S (1993–2015). "Mitochondrial DNA-Associated Leigh Syndrome and NARP". In Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong CT, Smith RJ, Stephens K. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle.
  7. ^ a b La Morgia C, Caporali L, Gandini F, Olivieri A, Toni F, Nassetti S, Brunetto D, Stipa C, Scaduto C, Parmeggiani A, Tonon C, Lodi R, Torroni A, Carelli V (2014). "Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions". BMC Neurology. 14: 116. doi:10.1186/1471-2377-14-116. PMC 4047257. PMID 24884847.
  8. ^ a b Flaquer A, Baumbach C, Kriebel J, Meitinger T, Peters A, Waldenberger M, Grallert H, Strauch K (2014). "Mitochondrial genetic variants identified to be associated with BMI in adults". PLOS ONE. 9 (8): e105116. doi:10.1371/journal.pone.0105116. PMC 4143221. PMID 25153900.
  9. ^ 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 (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.
  10. ^ "Mitochondrially encoded NADH dehydrogenase 2". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  11. ^ "MT-ND2 - NADH-ubiquinone oxidoreductase chain 2 - Homo sapiens (Human)". a hub for protein information. The UniProt Consortium.

Further reading[edit]

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