The bridge-like lipid transfer protein Vps13 are required for NVJ integrity and nucleophagy

Bridge-like lipid transfer proteins (BLTPs) constitute a superfamily of proteins localized at various intracellular membrane contact sites (MCSs). Members of this family have been implicated in human neurological disorders. Among them, the BLTP Atg2 is essential for the expansion of isolation membranes in macroautophagy. In this study, we demonstrate that another BLTP, Vps13, is involved in microautophagy in budding yeast. Nucleophagy-the autophagic degradation of nuclear components-is crucial for maintaining nuclear proteostasis, and its dysfunction has been linked to neurodegenerative diseases. In micronucleophagy, a portion of the nucleus is directly engulfed by the vacuolar membrane at the nucleus-vacuole junction (NVJ), followed by degradation within the vacuole. Vps13 accumulates at the NVJ upon inactivation of the target of rapamycin complex 1 (TORC1), a process necessary for NVJ integrity. Vps13 is essential for both micronucleophagy and cell viability under nutrient-deprived conditions. Its localization to the NVJ and lipid transfer activity are both critical for nucleophagy. Taken together, these findings suggest that the bridging and lipid transfer functions of Vps13 are both required for effective nucleophagy. This study uncovers novel physiological roles of Vps13 during starvation.