NDUFB8

NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial is an is_associated_with::enzyme that in humans is encoded by the NDUFB8 is_associated_with::gene. NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8 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 NDUFB8 gene is located on the q arm of is_associated_with::chromosome 10 in position 24.31 and is 6,194 base pairs long.

Structure
The NDUFB8 protein weighs 22 kDa and is composed of 186 amino acids. NDUFB8 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. is_associated_with::NDUFB7 and NDUFB8 have been shown to localize at the intermembrane surface of is_associated_with::complex I. 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.

Model organisms
is_associated_with::Model organisms have been used in the study of NDUFB8 function. A conditional is_associated_with::knockout mouse line called Ndufb8tm1a(EUCOMM)Wtsi was generated at the is_associated_with::Wellcome Trust Sanger Institute. Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping