Shinoda, S. | bioRxiv Science

bioRxiv2026

Msc1 facilitates glucose starvation-induced remodeling of the nucleus-vacuole junction

The nucleus-vacuole junction (NVJ) is a membrane contact site between the nuclear envelope and the vacuole in yeast that undergoes dynamic remodeling in response to nutrient starvation. Here, we report that Msc1 is a glucose starvation (GS)-responsive NVJ factor. GS strongly induced Msc1 expression and promoted its accumulation at the NVJ. Although Msc1 is not essential for NVJ formation itself, loss of Msc1 impaired GS-dependent functional maturation of the NVJ, including stabilization and recruitment of multiple NVJ-associated proteins. Notably, GS-induced transcriptional activation of NVJ1 was markedly attenuated in msc1{Delta} cells, suggesting that proper NVJ remodeling contributes to the execution of stress-responsive transcriptional programs. Together, these findings establish Msc1 as an upstream regulator linking GS to functional remodeling of the NVJ and associated transcriptional responses.

cell biology↗

bioRxiv2023

Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation

During macroautophagy, cytoplasmic constituents are engulfed by autophagosomes. Lysosomes fuse with closed autophagosomes but not with unclosed intermediate structures. This is achieved in part by the late recruitment of the autophagosomal SNARE syntaxin 17 (STX17) to mature autophagosomes. However, how STX17 recognizes autophagosome maturation is not known. Here, we show that this temporally regulated recruitment of STX17 depends on the positively charged C-terminal region of STX17. Consistent with this finding, mature autophagosomes are more negatively charged compared with unclosed intermediate structures. This electrostatic maturation of autophagosomes is likely driven by the accumulation of phosphatidylinositol 4-phosphate (PI4P) in the autophagosomal membrane. Accordingly, dephosphorylation of autophagosomal PI4P prevents the association of STX17 to autophagosomes. Furthermore, molecular dynamics simulations support PI4P-dependent membrane insertion of the transmembrane helices of STX17. Based on these findings, we propose a model in which STX17 recruitment to mature autophagosomes is temporally regulated by a PI4P-driven change in the surface charge of autophagosomes.

cell biology↗