The Ume6-Sin3-Rpd3 complex regulates ATG8 transcription to control autophagosome size

Abstract

The vast majority of studies addressing the induction of autophagy have focused upon cytoplasmic aspects of its regulation. Recently, we have started to expand our knowledge regarding the nuclear events of autophagic induction. Many autophagy-related genes are transcriptionally upregulated upon induction of autophagy, but only in a limited number of cases do we know the pathways leading to this upregulation. Few transcription factors have been implicated in controlling autophagy genes in yeast. However, many of the ATG genes show some level of transcriptional induction upon starvation. Now, we show that transcription of ATG8 is repressed under growing conditions by the Ume6-Sin3-Rpd3 complex.

Figure 1. Schematic model for Ume6-dependent regulation of ATG8 transcription. In growing conditions, upstream kinase sensors such as PKA inhibit the Rim15 kinase; active Ume6 keeps ATG8 transcription at a low basal level, which is adequate for the production of enough Atg8 to make relatively small Cvt vesicles. Under starvation conditions, PKA activity is inhibited and the now active Rim15 phosphorylates and inhibits Ume6, resulting in a higher level of ATG8 transcription; the subsequently increased amount of Atg8 allows the generation of large autophagosomes.