Selective autophagy in budding yeast

Abstract

Autophagy is a bulk degradation system, widely conserved in eukaryotes. Upon starvation, autophagosomes enclose a portion of the cytoplasm and ultimately fuse with the vacuole. The contents of autophagosomes are degraded in the vacuole, and recycled to maintain the intracellular amino-acid pool required for protein synthesis and survival under starvation conditions. Previously, autophagy was thought to be an essentially nonselective pathway, but recent evidence suggests that autophagosomes carry selected cargoes. These studies have identified two categories of selective autophagy - one highly selective and dependent on autophagy-related 11 (Atg11); another, less selective, that is, independent of Atg11. The former, selective category comprises the Cvt pathway, mitophagy, pexophagy and piecemeal microautophagy of the nucleus; acetaldehyde dehydrogenase 6 degradation and ribophagy belong to the latter, less selective category. In this review, I focus on the mechanisms and the physiological roles of these selective types of autophagy.

Figure 1

Schematic of the Cvt complex. The Cvt complex is localized near the vacuole in S. cerevisiae (left panel). Ty1 VLPs (gray) are associated with the Ape1 complex, the main component of the Cvt complex (dark gray). These two structures can be observed by electron microscopy

Figure 2

Multiple pathways of selective autophagy. (a) Atg11 is a key component of a number of selective autophagy routes, including the Cvt pathway, mitophagy, pexophagy and PMN. By contrast, Atg11 is dispensable for ribophagy and preferential Ald6 degradation. ‘Core' Atg proteins function in the membrane biogenesis of Cvt vesicles/autophagosomes. (b) Schematic of Atg11-dependent selective autophagy. Atg11 functions as a scaffold protein for PAS formation by recruiting core Atg proteins. Autophagosomes are generated from the PAS and, subsequently, delivered to the vacuole, where the selected cargoes are degraded

Figure 3

Two modes of pexophagy. When methylotrophic yeasts are grown in a methanol-containing medium, peroxisomes develop and form a cluster. Transferring the cells to glucose medium induces a process called micropexophagy, whereby the vacuolar membrane begins to enwrap the whole cluster (top). Subsequently, a cup-shaped membrane structure, the MIPA, emerges on the open surface of the peroxisome cluster. Transfer from methanol to an ethanol-containing medium induces a process called macropexophagy, during which, peroxisomes are enclosed in autophagosomes, termed pexophagosomes, and delivered to the vacuole one by one (bottom)

Figure 4

Differentiation of C. orbiculare during host invasion. Macroautophagy is required for germination and development of the appressorium from the conidium (asexual spore). Pexophagy in the appressorium is necessary for the subsequent development of the invasive hypha