The central stalk of the ATP synthase is an elongated hetero-oligomeric structure, providing a physical connection between the catalytic sites in F1 and the proton translocation channel in F0 for energy transduction between the two subdomains. The shape of the central stalk and relevance to energy coupling is essentially the same in ATP synthases from all forms of life, yet the protein composition of this domain changed during evolution of the mitochondrial enzyme from a two-subunit to three-subunit structure (gamma,delta,epsilon). Whereas the mitochondrial gamma and delta-subunits are homologues of the bacterial central stalk proteins, the deliberate addition of subunit epsilon remains poorly understood. Here we report that down-regulation of the gene (ATP15) encoding epsilon-subunit rapidly leads to lethal F0-mediated proton leaks through the membrane because of the loss of stability of the ATP synthase. The epsilon-subunit is thus essential for oxidative phosphorylation. Moreover, mutations in F0 subunits a and c that slow the proton translocation rate were identified that prevent epsilon-deficient ATP synthases from dissipating the electrochemical potential. Cumulatively, our data lead us to propose that the epsilon-subunit evolved to permit operation of the central stalk under the torque imposed at the normal speed of proton movement through mitochondrial F0.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|