Autophagy is induced during cell death by incompatibility and is essential for differentiation in the filamentous fungus Podospora anserina

Abstract

SummaryIn filamentous fungi, a cell death reaction occurs when cells of unlike genotype fuse. This cell death reaction, known as incompatibility reaction, is genetically controlled by a set of loci termed het loci (for heterokaryon incompatibility loci). In Podospora anserina , genes induced during this cell death reaction ( idi genes) have been identified. The idi-6/pspA gene encodes a serine protease that is the orthologue of the vacuolar protease B of Saccharomyces cerevisiae involved in autophagy. We report here that the PSPA protease participates in the degradative autophagic pathway in Podospora . We have identified the Podospora orthologue of the AUT7 gene of S. cerevisiae involved in the early steps of autophagy in yeast. This gene is induced during the development of the incompatibility reaction and was designated idi-7 . We have used a GFP-IDI7 fusion protein as a cytological marker of the induction of autophagy. Relocalization of this fusion protein and detection of autophagic bodies inside the vacuoles during the development of the incompatibility reaction provide cytological evidence of induction of autophagy during this cell death reaction. Therefore, cell death by incompatibility in fungi appears to be related to type II programmed cell death in metazoans. In addition, we found that pspA and idi-7 null mutations confer differentiation defects such as the absence of female reproductive structures, indicating that autophagy is required for differentiation in Podospora .

Functional Analysis of the ATG8 Homologue Ao atg8 and Role of Autophagy in Differentiation and Germination in Aspergillus oryzae

“…S. cerevisiae Atg8 is an essential protein in the autophagic pathway, and orthologues of Atg8 in other organisms have been used as specific markers of autophagy (8,19,27,35). In order to isolate the A. oryzae ATG8 gene homologue, we searched the A. oryzae EST and genome databases using the BLAST algorithm.…”

“…In P. anserina, ⌬idi-7/⌬PaATG8 mutants show defects in the differentiation of aerial hyphae and the protoperithecia, which is a female reproductive organ (27). By contrast, A. oryzae has no sexual reproduction, and conidia are the sole reproductive organs.…”

“…Additionally, in Caenorhabditis elegans, atg mutations result in abnormal dauer development, which is also induced by starvation, overcrowding, high temperature and so on (17). Recent studies have suggested that autophagy might participate in diseases such as cancer, liver disease, muscular disorder, and neurodegeneration (31) and protect from infection by bacterial pathogens (e.g., group A Streptococcus and Shigella) (20,22).In filamentous fungi, the processes of autophagy have been observed and studied for Podospora anserina (26,27). In this species, autophagy is induced during cell death by incompatibility, which occurs when cells of different genotypes fuse.…”

“…In filamentous fungi, the processes of autophagy have been observed and studied for Podospora anserina (26,27). In this species, autophagy is induced during cell death by incompatibility, which occurs when cells of different genotypes fuse.…”

“…In this species, autophagy is induced during cell death by incompatibility, which occurs when cells of different genotypes fuse. Null mutants of the idi-7/PaATG8 gene (the orthologue of S. cerevisiae ATG8) form fewer aerial hyphae and no protoperithecia (27). Furthermore, a null mutant of PaATG1 (the orthologue of S. cerevisiae ATG1) shows the same defects as those of the ⌬idi-7/PaATG8 mutants (26).…”