NDUFAF2

NDUFAF2 is a protein that in humans is encoded by the NDUFAF2 gene. The protein is a member of the complex I assembly (MCIA) complex, which is involved in the assembly of complex I of the mitochondrial respiratory chain. This complex is the first enzyme of the mitochondrial electron transport chain, which uses energy from electrons to transport protons across the inner mitochondrial membrane, generating a proton gradient that drives ATP synthesis.

Function

NDUFAF2 is an assembly factor for the mitochondrial respiratory chain complex I, 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.

Clinical significance

Mutations in the NDUFAF2 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

• Mitochondrial diseases
• Mitochondrial myopathy
• Leigh syndrome
• Leber hereditary optic neuropathy
• Parkinson's disease