Autophagy and organelle quality control

Autophagy is a conserved degradation and recycling pathway in which eukaryotic cells deliver their own proteins and organelles to the vacuole. In macroautophagy the cargo is enclosed in double-membrane vesicles, the autophagosomes, which then fuse with the vacuole. Non-selective (bulk) autophagy engulfs portions of the cytoplasm at random, typically in response to starvation or stress. In selective autophagy, cargo receptors recognize specific cargos such as organelles, protein aggregates or enzymes and direct them into autophagosomes.
In filamentous ascomycetes, autophagy is involved in many developmental processes. Using reverse genetics, we showed that the core autophagic machinery is needed for multicellular development in S. macrospora: SmATG8 and SmATG4 are required for fruiting-body development, vegetative growth and ascospore germination, and SmATG12 is required for fruiting-body formation. Other components are indispensable: SmATG7 and the kinases SmVPS34 and SmVPS15 are required for viability. The bZIP transcription factor SmJLB1 regulates the autophagy genes Smatg8 and Smatg4.
Our present work concentrates on selective autophagy. We identified SmNBR1, the homolog of the human cargo receptor NBR1, and showed that it is involved in the selective degradation of peroxisomes (pexophagy). A tagged version of human NBR1 can functionally replace the fungal protein, which shows how conserved this receptor is.
Organelles are also kept functional by other quality-control systems. The Lon protease SmLON2 is located mainly in glyoxysomes; a mutant lacking SmLON2 forms fewer fruiting bodies and ascospores and cannot grow under mild oxidative stress. SmVAC14, the scaffold protein of the Fab1/PIKfyve complex, is important for vacuolar size and morphology, for sexual development and for the response to starvation.
Our aim is to understand how selective autophagy and organelle quality control contribute to vegetative growth and fruiting-body development: which cargos are degraded, how they are recognized, and at which stage of development this is needed.