NDUFA5

Structure

The NDUFA5 gene is located on the q arm of chromosome 7 and it spans 64,655 base pairs. NDUFA5 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.

Function

The human NDUFA5 gene codes for the B13 subunit of complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. The NDUFA5 protein localizes to the mitochondrial inner membrane and it is thought to aid in this transfer of electrons. Initially, NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the 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 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

NDUFA5, ATP5A1 and ATP5A1 all show consistently reduced expression in brains of autism patients. Mitochondrial dysfunction and impaired ATP synthesis can result in oxidative stress, which may play a role in the development of autism.{{Cite journal

Interactions

NDUFA5 has many protein-protein interactions, such as ubiquitin C and with members of the NADH dehydrogenase [ubiquinone] 1 beta subcomplex, including NDUFB1, NDUFB9 and NDUFB10.

References

References

1. "Entrez Gene: NDUFA5 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5".
2. (2013). "Fundamentals of biochemistry : life at the molecular level". Wiley.
3. (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research.
4. "NDUFA5 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
5. (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenet Cell Genet.