The mitochondrial ATP synthase complex synthesizes ATP from ADP and Pi, utilizing energy generated by the electron transport chain. In mammalian cells this multisubunit enzyme complex is composed of approximately 13 different polypeptide subunits. Two of these subunits are encoded by the mitochondrial genome, whereas the rest of the subunits are encoded by nuclear genes, synthesized on cytoplasmic ribosomes, and imported into the mitochondria. At least three of the subunits of the ATP synthase complex (including the alpha, beta, and proteolipid subunits) are encoded by multiple nuclear genes in higher eucaryotes. The long term objectives of this study are to determine the number, structure, expression, and, ultimately, the regulation of the genes that encode subunits of the mammalian ATP synthase complex and to examine the structure and function of the proteins encoded by these genes.
The specific aims of the research described in this proposal are: (1) To isolate and characterize cDNAs that encode each of the isoforms of the alpha- and beta-subunits of the bovine mitochondrial ATP synthase complex. (2) To analyze the number, size, and abundance of the alpha- and beta-subunit isoform mRNAs in different tissues and at different stages of development. (3) To examine the tissue distribution of the alpha- and beta- subunit isoform polypeptides. (4) To isolate the genes that encode each of the alpha- and beta- subunit isoforms, to examine their organization, expression and chromosomal location. A complete understanding of the structure, function, and regulation of each of the components of the mammalian ATP synthase complex is essential since this enzyme its fundamental to all aspects of cellular life.
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