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.
Keywords: ESCRT; Microautophagy; PI(3,5)P2; PROPPIN; TORC1; Vps4.
Copyright © 2024 Elsevier Inc. All rights reserved.