Abstract:
RATIONALE:We previously discovered several phosphorylations to the beta subunit of the mitochondrial F(1)F(o) ATP synthase complex in isolated rabbit myocytes on adenosine treatment, an agent that induces cardioprotection. The role of these phosphorylations is unknown. OBJECTIVE:The present study focuses on the functional consequences of phosphorylation of the ATP synthase complex beta subunit by generating nonphosphorylatable and phosphomimetic analogs in a model system, Saccharomyces cerevisiae. METHODS AND RESULTS:The 4 amino acid residues with homology in yeast (T58, S213, T262, and T318) were studied with respect to growth, complex and supercomplex formation, and enzymatic activity (ATPase rate). The most striking mutant was the T262 site, for which the phosphomimetic (T262E) abolished activity, whereas the nonphosphorylatable strain (T262A) had an ATPase rate equivalent to wild type. Although T262E, like all of the beta subunit mutants, was able to form the intact complex (F(1)F(o)), this strain lacked a free F(1) component found in wild-type and had a corresponding increase of lower-molecular-weight forms of the protein, indicating an assembly/stability defect. In addition, the ATPase activity was reduced but not abolished with the phosphomimetic mutation at T58, a site that altered the formation/maintenance of dimers of the F(1)F(o) ATP synthase complex. CONCLUSIONS:Taken together, these data show that pseudophosphorylation of specific amino acid residues can have separate and distinctive effects on the F(1)F(o) ATP synthase complex, suggesting the possibility that several of the phosphorylations observed in the rabbit heart can have structural and functional consequences to the F(1)F(o) ATP synthase complex.
journal_name
Circ Resjournal_title
Circulation researchauthors
Kane LA,Youngman MJ,Jensen RE,Van Eyk JEdoi
10.1161/CIRCRESAHA.109.214155subject
Has Abstractpub_date
2010-02-19 00:00:00pages
504-13issue
3eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.109.214155journal_volume
106pub_type
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