Autophagy in unicellular eukaryotes

Abstract

Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.

Figure 1.

Macro- and microautophagy in yeast. (a) Schematic representation of macroautophagy in baker's yeast. Upon induction of (nitrogen) starvation, the PAS (pre-autophagosomal structure or phagophore assembly site) incorporates membrane material and grows out to become the double membrane-layered phagophore that randomly sequesters cytoplasmic components (proteins and organelles). After complete engulfment of the cytoplasmic material, an autophagosome is formed. Subsequently, the outer membrane of the autophagosome fuses with the vacuolar membrane. As a result, this membrane obtains vacuolar characteristics (red colour) and ultimately becomes part of the vacuolar membrane, thereby increasing the size of the organelle. Additionally, a single membrane-bound autophagic body enters the vacuole, where it will become degraded by vacuolar hydrolases. (b) Schematic representation of microautophagy in baker's yeast. During microautophagy, the membrane of the vacuole engulfs a portion of the cytoplasm (including organelles). As a result, a vesicle with a single membrane originating from the vacuolar membrane (red colour) is formed inside the vacuole. This contrasts to macroautophagy, where the membrane of the autophagic body originates from the autophagosome (black colour). After complete engulfment, the vesicle and its contents are degraded by vacuolar hydrolases. Consequently, during microautophagy, the size of the vacuolar membrane is reduced. During selective forms of autophagy, mechanisms similar to macro- and microautophagy are used to selectively package peroxisomes, mitochondria, endoplasmic reticulum, ribosomes and portions of the nucleus (see text for details).

Figure 2.

The core autophagy machinery. Schematic representation of the two Ub-like conjugation systems that drive phagophore enlargement by forming Atg8-PE and the Atg5=Atg12/Atg16 complex. The numbers refer to Atg proteins. Specific amino acid residues required for the conjugation reactions are indicated in the one-letter code. The asterisks indicate the Atg7 activated forms of the Ub-like proteins Atg8 and Atg12. PE, phosphatidylethanolamine. For details, see text.