Atg1, a key regulator of autophagy, functions to promote MAPK activation and cell death upon calcium overload in fission yeast.

Autophagy promotes or inhibits cell death depending on the environment and cell type. Our previous findings suggested that Atg1 is genetically involved in the regulation of Pmk1 MAPK in fission yeast. Here, we showed that Δ displays lower levels of Pmk1 MAPK phosphorylation than did the wild-type (WT) cells upon treatment with a 1,3-β-D-glucan synthase inhibitor micafungin or CaCl, both of which activate Pmk1. Moreover, the overproduction of Atg1, but not that of the kinase inactivating Atg1 activates Pmk1 without any extracellular stimuli, suggesting that Atg1 may promote Pmk1 MAPK signaling activation. Notably, the overproduction of Atg1 induces a toxic effect on the growth of WT cells and the deletion of Pmk1 failed to suppress the cell death induced by Atg1, indicating that the Atg1-mediated cell death requires additional mechanism(s) other than Pmk1 activation. Moreover, gene deletion induces tolerance to micafungin and CaCl, whereas deletion induces severe sensitivities to these compounds. The ΔΔ double mutants display intermediate sensitivities to these compounds, showing that deletion partly suppressed growth inhibition induced by Δ. Thus, Atg1 may act to promote cell death upon micafungin and CaCl stimuli regardless of Pmk1 MAPK activity. Since micafungin and CaCl are intracellular calcium inducers, our data reveal a novel role of the autophagy regulator Atg1 to induce cell death upon calcium overload independent of its role in Pmk1 MAPK activation.