Accelerated Cell Death in <i>Podospora</i> Autophagy Mutants

<jats:title>ABSTRACT</jats:title> <jats:p> Although autophagy is characteristic of type II programmed cell death (PCD), its role in cell death is currently debated. Both cell death-promoting and prosurvival roles of autophagy have been reported depending on the organism and the cell type. In filamentous fungi, a cell death reaction known as an incompatibility reaction occurs when cells of unlike genotype fuse. Cell death by incompatibility is characterized by a dramatic vacuolar enlargement and cell lysis. In <jats:italic>Podospora anserina</jats:italic> , autophagy is induced early during this cell death reaction. Cell death by incompatibility in <jats:italic>Podospora</jats:italic> is a model of type II PCD used here to assess the role of autophagy in this type of cell death. We have inactivated Pa <jats:italic>ATG1</jats:italic> , the <jats:italic>Podospora</jats:italic> ortholog of the <jats:italic>Saccharomyces cerevisiae ATG1</jats:italic> gene involved in the early steps of autophagy in yeast. The ΔPa <jats:italic>ATG1</jats:italic> mutant displays developmental defects characteristic of abrogated autophagy in <jats:italic>Podospora</jats:italic> . Using the green fluorescent protein-PaATG8 autophagosome marker, we show that autophagy is abolished in this mutant. Neither cell death by incompatibility nor vacuolization are suppressed in ΔPa <jats:italic>ATG1</jats:italic> and ΔPa <jats:italic>ATG8</jats:italic> autophagy mutants, indicating that a vacuolar cell death reaction without autophagy occurs in <jats:italic>Podospora</jats:italic> . Our results thus provide a novel example of a type II PCD reaction in which autophagy is not the cause of cell death. In addition, we found that cell death is accelerated in ΔPa <jats:italic>ATG</jats:italic> null mutants, suggesting that autophagy has a protective role in this type II PCD reaction. </jats:p>