File:Map of the human mitochondrial genome.svgLocation of the MT-ND5 gene in the human mitochondrial genome. MT-ND5 is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).
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, hydrophobictransmembrane 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]
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).[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]
↑Alston CL, Morak M, Reid C, Hargreaves IP, Pope SA, Land JM, Heales SJ, Horvath R, Mundy H, Taylor RW (February 2010). "A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy". Neuromuscular Disorders. 20 (2): 131–5. doi:10.1016/j.nmd.2009.10.010. PMID20018511.
↑Taylor RW, Morris AA, Hutchinson M, Turnbull DM (February 2002). "Leigh disease associated with a novel mitochondrial DNA ND5 mutation". European Journal of Human Genetics. 10 (2): 141–4. doi:10.1038/sj.ejhg.5200773. PMID11938446.
↑Naini AB, Lu J, Kaufmann P, Bernstein RA, Mancuso M, Bonilla E, Hirano M, DiMauro S (March 2005). "Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF". Archives of Neurology. 62 (3): 473–6. doi:10.1001/archneur.62.3.473. PMID15767514.
