MT-ND4

NADH-ubiquinone oxidoreductase chain 4 is a protein that in humans is encoded by the mitochondrial gene MT-ND4. The ND4 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. Variations in the MT-ND4 gene are associated with age-related macular degeneration (AMD), Leber's hereditary optic neuropathy (LHON), mesial temporal lobe epilepsy (MTLE) and cystic fibrosis.

Structure

The MT-ND4 gene is located in human mitochondrial DNA from base pair 10,760 to 12,137. An unusual feature of the human MT-ND4 gene is the 7-nucleotide gene overlap of its first three codons (5'-ATG CTA AAA-3' coding for amino acids Met-Leu-Lys) with the last three codons of the MT-ND4L gene (5'-CAA TGC TAA-3' coding for Gln, Cys and Stop). With respect to the MT-ND4L reading frame (+1), the MT-ND4 gene starts in the +3 reading frame: [CAA][TGC][TAA]AA versus CA[ATG][CTA][AAA].

The MT-ND4 gene produces a 52 kDa protein composed of 459 amino acids. MT-ND4 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-ND4 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.