Autophagy prevents runaway meiotic divisions

Abstract

In budding yeast, macroautophagy/autophagy is required for cells to enter into the meiotic divisions. Our recent publication showed that autophagy is also required for meiotic exit. Inhibition of autophagy as cells enter into the meiotic divisions results in additional rounds of spindle formation, spindle elongation, and aberrant chromosome segregation leading to cell death. Under these conditions, the meiosis II-specific cyclin Clb3 is absent, and two substrates of the anaphase-promoting complex/cyclosome (APC/C) persist into the additional divisions instead of being degraded after meiosis II. We found that the translational repressor Rim4 is a substrate of autophagy, which could explain these observations through its known role in repressing synthesis of Clb3 and the meiosis-specific co-activator of the APC/C, Ama1. Combined, these results provide new mechanistic insight into the control of meiotic exit through timed autophagic degradation of a master regulator of gene expression.

Keywords: APC/C; Atg1; Clb3; Rim4; autophagy; cyclins; meiosis.

Figure 1.

Model of meiotic chromosome segregation and the temporal regulation of Rim4’s autophagic degradation and release of mRNAs. Aggregated Rim4 binds CLB3, AMA1, and other mRNAs until meiosis II, when Rim4 is degraded by autophagy. The mRNAs are then translated for meiotic exit and spore formation.