ATP12 encodes a protein required for the assembly of mitochondrial ATP synthase 3. The ATP synthase complex utilizes proton motive force to generate ATP from ADP and P_i (4) and consists of two major components, soluble F₁ and membrane-bound F₀, each of which contains many subunits (5). The catalytic core of the enzyme resides in the F₁ component and consists of a hexamer of alternating alpha (Atp1p) and beta (Atp2p) subunits (6, 7). Although Atp12p binds selectively to the alpha subunit, it is not part of the ATP synthase complex. Instead, Atp12p binds to isolated alpha subunits in order to prevent alpha subunit aggregation prior to F₁ assembly. It is likely that Atp12p is displaced by the beta subunit during complex assembly (8). A second protein, Atp11p, functions in a similar manner to prevent aggregation of the beta subunit prior to F₁ assembly (3, 9).

Deletion of ATP12 leads to aggregation of alpha subunits and loss of F₁ assembly. Although ATP12 is required for the production of functional ATP synthase, it is not essential for cell viability. Like deletions in many genes necessary for the function or maintenance of mitochondria, loss of ATP12 leads to a "petite" phenotype; cells are slow-growing and unable to survive on nonfermentable carbon sources (3).

Orthologs of ATP12 have been found in eukaryotic cells that contain F₁ alpha and F₁ beta subunits (10). Orthologs have also been found in some bacteria but not in Arabidopsis or cyanobacteria (10). Mutation of human ATP12 leads to a decrease in the amount active ATP synthase (referred to as complex V) and the respiratory chain disorder ATPAF2 deficiency (2).

Last updated: 2006-11-10