Retrograde regulation: a novel path of communication between mitochondria, the nucleus, and peroxisomes in yeast

Alterations in mitochondrial function result in changes in nuclear gene expression, a process we have called retrograde regulation. Here we summarize studies on the effects of the mitochondrial state on expression of the CIT2 gene, which encodes citrate synthase 2, an enzyme that functions in the glyoxylate cycle and is located in peroxisomes. Various defective mitochondria result in up to a 30-fold transcriptional activation of the gene, a process which could provide additional citrate to mitochondria when the TCA cycle is limiting. We have identified three new genes, RTG1, RTG2, and RTG3, that are required for CIT2 expression. RTG1 and RTG3 encode basic helix-loop-helix transcription factors that bind, to the 5' flanking region of CIT2. RTG2 is a protein of unknown function. Both RTG1 and RTG2 are also required for oleic acid induction of peroxisomes. These studies reveal a complex pattern of interorganelle communication among mitochondria, the nucleus and peroxisomes.