NDUFA8
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 is an enzyme that in humans is encoded by the NDUFA8 gene. The NDUFA8 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. Structure. The NDUFA8 gene is located on the q arm of chromosome 9 in position 33.2 and spans 27,354 base pairs. The gene produces a 20 kDa protein composed of 172 amino acids. NDUFA8 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), 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 centers and the NADH binding site. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an 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 NADH dehydrogenase (ubiquinone ) complex at the inner mitochondrial membrane. NDUFA8 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I. The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal. Related pseudogenes have also been identified on four other chromosomes. Function. The human NDUFA8 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to  ubiquinone. NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH. 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 (CoQH). The flow of electrons changes the redox state of the protein, resulting in a conformational change and p"K" shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.