Role of NBR1-regulated selective autophagy in growth and development of filamentous fungi

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Autophagy literally implying “self-eating”, describes an evolutionarily conserved eukaryotic process of degradation and recycling within lysosomes in animals or vacuoles in plants and fungi. Two types of autophagy have been described: non-selective and selective autophagy. Non-selective autophagy is the random engulfment of cytoplasm and organelles into double-membrane vesicles, the autophagosomes, which deliver the cargo to the vacuole for degradation. In selective autophagy, specific cargos such as organelles, protein aggregates or enzymes are recognized by cargo receptors and enwrapped into autophagosomes. For sexual propagation, filamentous fungi produce three-dimensional fruiting bodies, where the sexual ascospores are generated. The homothallic (self-fertile) ascomycete Sordaria macrospora is an excellent fungal model organism to study multicellular fruiting-body development. In our previous studies, we had shown that non-selective autophagy is an essential and constitutively active process required to maintain high energy levels for filamentous growth and multicellular development in S. macrospora. However, the role of selective autophagy in the development of multicellular structures, such as fruiting bodies in filamentous ascomycetes has not yet been investigated in detail. We were able to demonstrate that a homolog of the mammalian selective cargo receptor Neighbor of BRCA1 (NBR1) Sm NBR1 acts as a receptor for pexophagy (selective degradation of peroxisomes) in S. macrospora. We established the SmNBR1-BioID method and confirmed that the BioID method is applicable in identifying new putative adaptor proteins linking SmNBR1 with diverse substrates. We aim to understand the mechanism and regulation of SmNBR1-mediated selective autophagy and in particular pexophagy in S. macrospora, and intend to provide insights into the role of selective autophagy in the development of filamentous fungi and higher eukaryotes.