We show here that SNF1 and SSN6 are required for derepression of the glucose-repressible yeast genes COX6 and CYC1, which encode the mitochondrial proteins cytochrome c oxidase subunit VI and iso-l-cytochrome c, respectively. In an snfl mutant genetic background, the transcription of both COX6 and CYC) continued to be repressed after cells were shifted into derepressing media. In an ssn6 mutant genetic background, both COX6 and CYCI were expressed constitutively at high levels in repressing media. SSN6 acted epistatically to SNFI in the regulation of both cytochrome genes. These findings are similar to previous findings on the effects of SNFI and SSN6 on SUC2 expression in Saccharomyces cerevisiae and are consistent with a model proposing that SNF1 exerts its effect through SSN6 on COX6 and CYCI.Yeast cells respond to growth in glucose by up-regulating fermentative metabolism, with the consequent production of ethanol. At the same time, enzymes in numerous metabolic pathways, including those involved in gluconeogenesis, the tricarboxylic acid cycle, and mitochondrial electron transport and oxidative phosphorylation (7, 9), are repressed. This process, referred to as glucose repression, is complex. It affects the activity of some enzymes and the synthesis of others (6-8, 13). For many genes, the effect of glucose repression on synthesis operates at the level of transcription (18,22) and is mediated by upstream cis-acting sites, i.e., upstream activation sequence elements (10,18,21,23).Through the isolation of nonrepressible and nonderepressible mutants and their suppressors, it has been possible to gain initial insight into the genetic regulation of glucose repression. Of the dozen or so genes so far implicated in glucose repression (1, 6-9, 13, 19), some of the best understood are SNFJ (CA TI, CCRI) and SSN6 (CYC8). The SNFJ gene (together with other SNF genes) (1-4, 15) is essential for sucrose fermentation because it is required for derepression of the synthesis of the secreted form of invertase, a product of SUC2. SNFJ also affects the derepression of a number of other glucose-repressible enzymes of intermediary metabolism; thus, it appears to be a global regulator of glucose repression (7,9 address the question, we studied COX6, (25, 26) and CYCI (11), the genes that encode cytochrome c oxidase subunit VI and iso-1-cytochrome c, respectively. Previous studies demonstrated that the transcription of both genes is glucose repressible in conjunction with the product of the HAP2 gene (11, 23). We report here that SNFI and SSN6 are also required for the release from glucose repression of COX6 and CYC1 and that they affect the transcription of these genes in a manner analogous to the way that they regulate SUC2.To determine whether SNFI is involved in COX6 regulation, we used an snfl deletion strain, MCY1595, and its parent carrying a wild-type SNFJ allele, MCY1093, kindly provided by Marian Carlson (Columbia University, New York, N.Y.). Cells were grown to the early log phase in 2% glucose, harvested, washed in H2...