ESCRT elicits vacuolar fission in the absence of Vps4 in budding yeast.

In budding yeast, endosomal sorting complex required for transport (ESCRT) mediates microautophagy by vacuolar membrane invagination into the vacuolar lumen, followed by Vps4-assisted membrane constriction and abscission. Here, we show that ESCRT elicits vacuolar fission in the absence of Vps4 after nutrient starvation, although vacuolar fusion is facilitated in wild-type cells in these conditions. ESCRT mediated vacuolar membrane invagination in vps4Δ cells, thereby causing vacuolar fission. It is known that vacuolar fission requires phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) and β-propellers that bind polyphosphoinositides (PROPPINs), PI(3,5)P2-binding proteins. However, PROPPIN, but not PI(3,5)P2, was dispensable for the ESCRT-mediated vacuolar fragmentation. Finally, we showed evidence that microlipophagy triggers vacuolar fission. Thus, disruption of the coordinated sequence of ESCRT-Vps4 operations in microautophagy leads to vacuolar fragmentation. This study provides insight into the ESCRT-Vps4 axis-dependent cellular disfunctions and related diseases.