F ₁ -dependent translation of mitochondrially encoded Atp6p and Atp8p subunits of yeast ATP synthase

Abstract

The ATP synthase of yeast mitochondria is composed of 17 different subunit polypeptides. We have screened a panel of ATP synthase mutants for impaired expression of Atp6p, Atp8p, and Atp9p, the only mitochondrially encoded subunits of ATP synthase. Our results show that translation of Atp6p and Atp8p is activated by F1 ATPase (or assembly intermediates thereof). Mutants lacking the ␣ or ␤ subunits of F1, or the Atp11p and Atp12p chaperones that promote F1 assembly, have normal levels of the bicistronic ATP8/ATP6 mRNAs but fail to synthesize Atp6p and Atp8p. F1 mutants are also unable to express ARG8 m when this normally nuclear gene is substituted for ATP6 or ATP8 in mitochondrial DNA. Translational activation by F1 is also supported by the ability of ATP22, an Atp6p-specific translation factor, to restore Atp6p and to a lesser degree Atp8p synthesis in the absence of F1. These results establish a mechanism by which expression of ATP6 and ATP8 is translationally regulated by F1 to achieve a balanced output of two compartmentally separated sets of ATP synthase genes.F1-ATPase ͉ mitochondria ͉ Saccharomyces cerevisiae ͉ translational regulation

Characterization of Gtf1p, the Connector Subunit of Yeast Mitochondrial tRNA-dependent Amidotransferase

“…2D). Similarly, other studies have shown Cox2p to be normally translated in an atp8 null mutant (36). This indicates that formation of Cox2p* is not dependent on the absence of Atp8p.…”

Assembly of the Rotor Component of Yeast Mitochondrial ATP Synthase Is Enhanced When Atp9p Is Supplied by Atp9p-Cox6p Complexes

“…Similarly, translation of the Atp6p and Atp8p subunits of ATP synthase on mitochondrial ribosomes is activated by F 1 ATPase or partially assembled F 1 (12). Both regulatory mechanisms achieve a balanced expression of the mitochondrial gene product(s) relative to partner proteins derived from the nucleo-cytoplasmic system.…”

Mechanisms of mitochondrial translational regulation

“…4). Indeed, Atp6 and Atp8 synthesis is dramatically decreased in null mutants of the a (atp1) and b (atp2) F 1 subunits or the Atp11 and Atp12 chaperones required for their assembly (10). The observed translational defect is not owing to transcriptional impairment, mRNA instability or mRNA processing inefficiency as the mature ATP6 and ATP8 mRNAs accumulate at wild-type level in the mutant strains (10).…”

“…At the beginning of the last decade, a CES mechanism was identified that translationally controls the expression of Cox1 in yeast mitochondria (8,9). More recently, translational regulation of Atp6, Atp8 and Cytb has been also reported (10,11).…”

“…Recently, Rak and Tzagoloff (10) reported that in yeast mitochondria the translation of ATP6 and ATP8 genes, but not ATP9, is dependent on the status of the F 1 ATPase assembly (Fig. 4).…”