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Autophagy was originally identified as a cytoprotective system that provides emergency backup energy and basic building blocks under starvation condition by digesting self components. Recent advances in the field unveiled that this system also protects cells against multiple types of stress, as well as invasion by pathogens. Consistent with these findings, autophagy has been redefined as a safeguard system that plays a vital role in human pathology, and this realization has led to exponential progress in autophagy research. In this review, we introduce the basic mechanisms of canonical autophagy and also discuss selective autophagy, a set of pathways that target specific cellular components for digestion; in particular, we focus on lysophagy, a recently identified mechanism required for lysosomal homeostasis. [ABSTRACT FROM AUTHOR]

In yeast, the selective autophagy of intracellular lipid droplets (LDs) or lipophagy can be induced by either nitrogen (N) starvation or carbon limitation (e.g., in the stationary (S) phase). We developed the yeast, Komagataella phaffii (formerly Pichia pastoris), as a new lipophagy model and compared the N-starvation and S-phase lipophagy in over 30 autophagy-related mutants using the Erg6-GFP processing assay. Surprisingly, two lipophagy pathways had hardly overlapping stringent molecular requirements. While the N-starvation lipophagy strictly depended on the core autophagic machinery (Atg1-Atg9, Atg18, and Vps15), vacuole fusion machinery (Vam7 and Ypt7), and vacuolar proteolysis (proteinases A and B), only Atg6 and proteinases A and B were essential for the S-phase lipophagy. The rest of the proteins were only partially required in the S-phase. Moreover, we isolated the prl1 (for the positive regulator of lipophagy 1) mutant affected in the S-phase lipophagy, but not N-starvation lipophagy. The prl1 defect was at a stage of delivery of the LDs from the cytoplasm to the vacuole, further supporting the mechanistically different nature of the two lipophagy pathways. Taken together, our results suggest that N-starvation and S-phase lipophagy have distinct molecular mechanisms. [ABSTRACT FROM AUTHOR]