Control of yeast and mammalian mitochondrial protein synthesis by cytoplasmic factors

Abstract

The biogenesis of the mitochondrial inner membrane requires the synthesis of proteins at 2 intracellular sites: 1 cytoplasmic; 1 mitochondrial. A mechanism must exist to coordinate the synthesis of proteins at the 2 distinct intracellular sites such that mitochondrial formation occurs in an orderly manner. Previous studies in yeast using selective inhibitors of cytoplasmic and mitochondrial protein synthesis have suggested that cytoplasmically synthesized proteins may control mitochondrial protein synthesis both in vivo [l-4] and in vitro [3] and that this control may occur by either stimulation of chain initiation or increased formation of mitochondrial mRNAs [5]. In [6] protein synthesis by yeast mitochondria in vitro was reported stimulated by addition of a high-speed cytoplasmic supernatant from yeast [6]. This effect is not species-specific, as protein synthesis in vitro by isolated yeast mitochondria could be stimulated markedly by post-polysomal supernatants from either E. coli, rat liver or yeast [7]. However, stimulation of yeast mitochondrial protein synthesis by all of these high speed supernatants may be due to the presence of non-dialyzable GMP which is converted to GDP (or GTP) during the incubation in the protein-synthesizing medium [8]. We have confirmed that GTP stimulates yeast mitochondrial protein synthesis in vitro, but addition of a post-polysomal supernatant from yeast doubles the rate of mitochondrial protein synthesis in