RTG genes in 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, such as in petites, the CIT2 gene encoding the peroxisomal glyoxylate cycle enzyme, citrate synthase 2 (CS2), is transcriptionally activated by as much as 30-fold, a phenomenon we call retrograde regulation. Two genes, RTG1 and RTG2, are required for both basal and elevated expression of CIT2 (Liao, X., and Butow, R. A. (1993) Cell 72, 61-71). Different blocks in the tricarboxylic acid cycle also elicit an increase in CIT2 expression, but not to the extent observed in petites. We have examined whether other genes of the glyoxylate cycle exhibit retrograde regulation and the role of RTG1 and RTG2 in their expression. Of the glyoxylate 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. Surprisingly, RTG1 and RTG2 are required for efficient growth of cells on medium containing oleic acid, a condition which induces peroxisome biogenesis; these genes are also required together for oleic acid induction 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 that, in addition to their role in retrograde regulation of CIT2, the RTG genes are important for expression of genes encoding peroxisomal proteins and are thus key components in a novel, three-way path of communication between mitochondria, the nucleus, and peroxisomes.
Chelstowska
A
A
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Butow
R A
RA
D000483:Alleles; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002467:Cell Nucleus / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000235:genetics; D002952:Citric Acid Cycle; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D008291:Malate Dehydrogenase / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008830:Microbodies / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009829:Oleic Acids; D012333:RNA, Messenger; C079378:RTG1 protein, S cerevisiae; C079379:RTG2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D019301:Oleic Acid; D008291:Malate Dehydrogenase; D002950:Citrate (si)-Synthase