NDUFB9

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 is an is_associated_with::enzyme that in humans is encoded by the NDUFB9 is_associated_with::gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 9 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.

Structure
The NDUFB9 gene is located on the q arm of is_associated_with::chromosome 8 in position 13.3 and is 10,884 base pairs long. The NDUFB9 protein weighs 22 kDa and is composed of 179 amino acids. NDUFB9 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. 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
A mutation in NDUFB9 resulting in reduction in NDUFB9 protein and both amount and activity of complex I has been shown to be a causal mutation leading to is_associated_with::Complex I deficiency.