De-phosphorylation of Atg13 by Cdc14 functions as a molecular switch for meiosis-specific autophagy oscillation Authors: Wenzhi Feng, Fei Wang* Affiliations: UT Southwestern Medical Center, Department of Internal Medicine, Center for Autophagy Research, Dallas, TX Abstract Autophagy is a conserved eukaryotic lysosomal degradation pathway, on which the signals from various signaling pathways can merge for cell to respond to dynamic changes of internal and external environments. Autophagy regulation is linked to literally every aspect of biology, and remains unknown in the field of meiosis, a specialized cell cycle in all sexual reproducing organisms. Using S. cerevisiae as model system, we have recently reported that autophagy is essential for meiosis exit. With combined genetic, biochemical and cell biological approaches, we reported here a striking pattern of autophagy during meiotic cell division: it oscillates, with peaks at Anaphase I (meiosis I exit) and Anaphase II (meiosis II exit). Importantly, we identified that Cdc14, an essential and conserved phosphatase that is periodically released from nucleus into cytosol at Anaphase I & Anaphase II to counteract Cdc28 (yeast CDK1) kinase activity so that meiosis exit and cytokinesis can be achieved, is responsible for autophagy oscillation. To elucidate the underlying molecular mechanism, we reconstituted in vitro three sequential events: the Cdc14 mediated Atg13p de-phosphorylation, de-phosphorylated Atg13 binding to Atg1, and Atg1 kinase activation. We conclude that Cdc14 stimulates autophagy at least through Atg1 activation. We further demonstrated that Cdc14 is a meiosis-specific autophagy regulator. These findings illustrate a novel meiotic pathway of Cdc14 that enables autophagy oscillation, while the physiological role(s) of autophagy oscillation remains to be explored.