Pexophagy: The Selective Degradation of Peroxisomes
Figure 4
Micropexophagy and macropexophagy. (a) Micropexophagy differs from macropexophagy in vacuole dynamics and formation of the MIPA instead of the pexophagosome. A pexophagy-specific PAS, required for both forms of pexophagy, is characterized by its localization near the peroxisome and also touching the vacuolar membrane. Micropexophagy can target a peroxisome cluster for degradation by vacuole remodeling to form cup-like vacuolar sequestration membranes (VSMs) and a lid-like cover called the MIPA (micropexophagy-specific membrane apparatus). Macropexophagy is characterized by individual sequestration of targeted peroxisomes into a pexophagosome, followed by its fusion with the vacuole for degradation and recycling. Pexophagy signaling is dependent on Mitogen-activated protein kinase (MAPK) pathways (Mid2-Slt2 cascade), but may also be triggered by internal (unknown) factors, including signals related to the status of, or metabolic need for, (e.g., damaged or superfluous) peroxisomes. (b) The upper panel depicts a single P. pastoris cell that has undergone peroxisome induction (in methanol) and has then been switched to micropexophagy conditions (glucose). The vacuole (red, FM 4–64) is shown surrounding the targeted peroxisome cluster (blue, BFP-SKL). The MIPA (green, GFP-Atg8) forms a lid over the cup-like VSMs. The lower panel illustrates pexophagosome formation around a single peroxisome under macropexophagy conditions (ethanol). (c) S. cerevisiae cell labeled with GFP-tagged thiolase (a peroxisome matrix marker) and vacuole marker (FM 4–64, red) shows proliferated peroxisomes under nutrient-rich conditions (in oleate, top panel). When the cells are switched to glucose without nitrogen, peroxisomes are targeted to the vacuole by macropexophagy and GFP accumulates in the vacuole (lower panel).
