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

自噬的字面意思是“自噬”，描述了一种进化上保守的真核生物降解和循环的过程，即动物体内的溶酶体或植物和真菌中的液泡。已经描述了两种类型的自噬：非选择性自噬和选择性自噬。非选择性自噬是指细胞质和细胞器随机吞噬成双膜小泡，即自噬小体，将货物运送到液泡进行降解。在选择性自噬中，特定的货物，如细胞器、蛋白质聚集体或酶，被Cargo受体识别并包裹到自噬小体中。对于有性繁殖，丝状真菌产生三维子实体，在那里产生有性子囊孢子。大孢子囊菌是研究多细胞子实体发育的优良真菌模式生物。在我们以前的研究中，我们已经证明了非选择性自噬是维持大孢子菌丝状生长和多细胞发育所需的高能量水平所必需的和结构性活跃的过程。然而，选择性自噬在丝状子囊菌的子实体等多细胞结构发育中的作用还没有得到详细的研究。我们能够证明，哺乳动物选择性货物受体BRCA1(NBR1)Sm NBR1的同源物作为大孢子链霉噬菌体(选择性降解过氧化物体)的受体。我们建立了SmNBR1-BioID方法，并证实该方法适用于鉴定连接SmNBR1与不同底物的新的可能的接头蛋白。我们的目的是了解SmNBR1介导的选择性自噬的机制和调控，特别是大孢子链霉菌中的自噬，并试图对选择性自噬在丝状真菌和高等真核生物发育中的作用提供见解。

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.