RTG GENES IS YEAST THAT FUNCTION IN COMMUNICATION BETWEEN MITOCHONDRIA AND THE NUCLEUS ARE ALSO REQUIRED FOR EXPRESSION OF GENES ENCODING PEROXISOMAL PROTEINS

In Saccharomyces cerevisiae cells with dysfunctional mitochondria, suc h as in petites, the CIT2 gene encoding the peroxisomal glyoxylate cyc le enzyme, citrate synthase 2 (CS2), is transcriptionally activated by as much as 30-fold, a phenomenon we call retrograde regulation. Two g enes, RTG1 and RTG2, are required for both basal and elevated expressi on of CIT2 (Liao, X, and Butow, R. A. (1993) Cell 72, 61-71). Differen t blocks in the tricarboxylic acid cycle also elicit an increase in CI T2 expression, but not to the extent observed in petites. We have exam ined whether other genes of the glyoxylate cycle exhibit retrograde re gulation and the role of RTG1 and RTG2 in their expression. Of the gly oxylate cycle genes tested, CIT2 is the only one that shows retrograde regulation, suggesting that CS2 may be an important control point for metabolic cross-feeding from the glyoxylate cycle to mitochondria. Su rprisingly, RTG1 and RTG2 are required for efficient growth of cells o n medium containing oleic acid, a condition which induces peroxisome b iogenesis; these genes are also required together for oleic acid induc tion of three peroxisomal protein genes tested, POX1 and CTA1 involved beta-oxidation of long chain fatty acids and PMP27, which encodes the most abundant protein of peroxisomal membranes. These data indicate t hat, in addition to their role in retrograde regulation of CIT2, the R TG genes are important for expression of genes encoding peroxisomal pr oteins and are thus key components in a novel, three-way path of commu nication between mitochondria, the nucleus, and peroxisomes.