ORGANELLAR SIGNALING From Mitochondria to Nucleus

Abstract:

Expression of certain nuclear genes, such as CIT2, is regulated by the status of the mitochondria. In yeast, this pathway from mitochondria to nucleus, called the retrograde signaling pathway, involves the genes RTG1, RTG2, and RTG3 and can be stimulated in cells lacking mitochondrial DNA (^o). Rtg1p and Rtg3p are transcription factors that act as a heterodimer, and Rtg2p is a protein with an ATP-binding motif. The authors confirm that the dimerization of Rtg1p and Rtg3p is independent of Rtg2p and does not depend on mitochondrial status. Observation of GFP fusion proteins of Rtg1 and Rtg3 demonstrated that both proteins accumulate in the nucleus in ^o cells and that the nuclear accumulation is dependent on Rtg2p, which controls the dephosphorylation of Rtg3p. Deletion of RTG1 led to nuclear accumulation of Rtg3p in normal cells (⁺) suggesting that interaction with Rtg1p controls the cytosolic localization of the complex under normal conditions. Thus, the signal from the mitochondria to the nucleus involves regulation of the phosphorylation state of Rtg3p by Rtg2p and the subsequent nuclear accumulation of the Rtg1p-Rtg3p complex.

Sekito, T., Thornton, J., and Butow, R.A. (2000) Mitochondria-to-nuclear signaling is regulated by the subcellular localization of the transcription factors Rtg1p and Rtg3p. Mol. Biol. Cell 11: 2103-2115. [Abstract] [Full Text]