NDUFA11

NDUFA11 is a protein that in humans is encoded by the NDUFA11 gene. The 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.

Function

The NDUFA11 protein is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit and is not directly involved in the pathway of electron transfer. The complex 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:ubiquinone oxidoreductase complex at the inner mitochondrial membrane.

Clinical significance

Mutations in the NDUFA11 gene are associated with Mitochondrial complex I deficiency, a disorder of the mitochondrial respiratory chain that causes a wide range of clinical disorders, from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson's disease.

See also

• NADH dehydrogenase (ubiquinone)
• Mitochondrial complex I deficiency
• Leigh syndrome
• Leber hereditary optic neuropathy
• Parkinson's disease