A nucleus-vacuole junction in fission yeast enriches the HMG-CoA reductase Hmg1 and INSIG protein Ins1

Abstract

Membrane contact sites (MCSs) enable communication between organelles and play central roles in lipid metabolism. In budding yeast, the nucleus-vacuole junction (NVJ) functions as a dynamic platform that integrates lipid metabolism and stress responses. However, it remains unclear whether NVJ structure and function are broadly conserved across eukaryotes, particularly because Nvj1, the key membrane tethering factor that mediates NVJ formation in budding yeast, is absent in higher eukaryotes. Here, we investigated whether an MCS analogous to the NVJ in budding yeast exists in fission yeast (Schizosaccharomyces pombe), which lacks Nvj1. We show that an NVJ is present in fission yeast and serves as a platform for the accumulation of sterol synthesis factors, including the HMG-CoA reductase Hmg1 and the INSIG homolog Ins1. We further demonstrate that the localization of these factors depends on the membrane protein insertase Snd302 and is dynamically regulated by nutrient conditions. Our findings reveal that, despite the absence of Nvj1, the NVJ is functionally conserved as a site for sterol synthesis in fission yeast, suggesting a conserved role of spatial organization in lipid metabolism.