MT-ND5
Location of the MT-ND5 gene in the human mitochondrial genome. MT-ND5 is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).
NADH-ubiquinone oxidoreductase chain 5 is a protein that in humans is encoded by the mitochondrial gene MT-ND5.[2] 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.[3] 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).[4][5]
Structure
MT-ND5 is located in mitochondrial DNA from base pair 12,337 to 14,148.[2] The MT-ND5 gene produces a 67 kDa protein composed of 603 amino acids.[6][7] 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.[3]
Function
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).[8] 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.[3]
Clinical Significance
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.[4][5]
Interactions
MT-ND5 interacts with Glutamine synthetase (GLUL), LIG4 and YME1L1.[2]
References
- ↑ "Human PubMed Reference:".
- 1 2 3 "Entrez Gene: MT-ND5 NADH dehydrogenase subunit 5".
- 1 2 3 Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.
- 1 2 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.
- 1 2 "MT-ND5". Genetics Home Reference. US National Library of Medicine. Retrieved 23 March 2015.
- ↑ 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. - ↑ "NADH-ubiquinone oxidoreductase chain 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ↑ "MT-ND5 - NADH-ubiquinone oxidoreductase chain 5 - Homo sapiens (Human)". UniProt.org: a hub for protein information. The UniProt Consortium.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.