NDUFB6

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6, also known as complex I-B17, is a is_associated_with::protein that in humans is encoded by the NDUFB6 is_associated_with::gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 6, is an accessory subunit of the is_associated_with::NADH dehydrogenase (ubiquinone) complex, located in the is_associated_with::mitochondrial inner membrane. It is also known as is_associated_with::Complex I and is the largest of the five complexes of the is_associated_with::electron transport chain.

Gene
The NDUFB6 gene is located on the p arm of is_associated_with::chromosome 9 in position 21.1 and is 19,659 base pairs long.

Structure
The NDUFB6 protein weighs 17 kDa and is composed of 128 amino acids. NDUFB6 is a subunit of the enzyme is_associated_with::NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, is_associated_with::hydrophobic is_associated_with::transmembrane domain and a is_associated_with::hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an is_associated_with::alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the is_associated_with::NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane.

Function
The protein encoded by this gene is an accessory subunit of the multisubunit NADH:ubiquinone oxidoreductase (is_associated_with::complex I) that is not directly involved in catalysis. However, NDUFB6 is required for electron transfer activity. Mammalian complex I is composed of 45 different subunits. It locates at the is_associated_with::mitochondrial inner membrane. This protein complex has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the is_associated_with::respiratory chain. The immediate electron acceptor for the enzyme is believed to be is_associated_with::ubiquinone. is_associated_with::Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. Initially, is_associated_with::NADH binds to Complex I and transfers two electrons to the is_associated_with::isoalloxazine ring of the is_associated_with::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 is_associated_with::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.

Clinical significance
Decreased expression of genes involved in oxidative phosphorylation, including NDUFB6, is associated with is_associated_with::insulin resistance and is_associated_with::type 2 diabetes. A is_associated_with::polymorphism in the promoter region of the NDFUB6 gene resulting in an is_associated_with::adenine to is_associated_with::guanine shift at rs629566 was shown to create a DNA methylation site that is associated with a decline in NDUFB6 expression in muscle of aging patients.