Remodelling of Nucleus-Vacuole Junctions During Metabolic and Proteostatic Stress

Abstract

Cellular adaptation to stress and metabolic cues requires a coordinated response of different intracellular compartments, separated by semipermeable membranes. One way to facilitate interorganellar communication is via membrane contact sites, physical bridges between opposing organellar membranes formed by an array of tethering machineries. These contact sites are highly dynamic and establish an interconnected organellar network able to quickly respond to external and internal stress by changing size, abundance and molecular architecture. Here, we discuss recent work on nucleus-vacuole junctions, connecting yeast vacuoles with the nucleus. Appearing as small, single foci in mitotic cells, these contacts expand into one enlarged patch upon nutrient exhaustion and entry into quiescence or can be shaped into multiple large foci essential to sustain viability upon proteostatic stress at the nuclear envelope. We highlight the remarkable plasticity and rapid remodelling of these contact sites upon metabolic or proteostatic stress and their emerging importance for cellular fitness.

Niemann-Pick Type C Proteins Are Required for Sterol Transport and Appressorium-Mediated Plant Penetration of Colletotrichum orbiculare

“…NVJ formation depends on the nuclear membrane protein Nvj1 and the vacuolar membrane protein Vac8. NVJs allow the recruitment of proteins involved in lipid metabolism and transport and serve as a platform for lipid droplet biogenesis upon glucose restriction ( 56 ). NVJ components include the sterol-transfer protein Lam6 and the oxysterol-binding protein Osh1, suggesting its contribution to sterol homeostasis ( 56 ).…”

“…NVJs allow the recruitment of proteins involved in lipid metabolism and transport and serve as a platform for lipid droplet biogenesis upon glucose restriction ( 56 ). NVJ components include the sterol-transfer protein Lam6 and the oxysterol-binding protein Osh1, suggesting its contribution to sterol homeostasis ( 56 ). Although NPC proteins were not identified as the NVJ-associated proteins, interactions between NPC2, NPC1, and the ER integral membrane protein ORP5 suggested a potential mechanism for sterol transfer between endosome lumen and the ER in mammals ( 57 ).…”

Partitioning into ER membrane microdomains impacts autophagic protein turnover during cellular aging

“…This organellar contact is established by interactions of the integral nER protein Nvj1 with the armadillo repeat-containing protein Vac8, anchored to the vacuolar membrane via palmitoylation 41 . This tethering pair provides a multi-functional platform for the recruitment of additional contact site components, most of them involved in lipid metabolism 42 . For instance, the sterol transporter Lam6 is targeted to the NVJs by association with Vac8 43 , and the recruitment of Snd3 and Osh1 to the contact sites depends on interactions with the cytoplasmic domain of Nvj1 [44][45][46] .…”

Changing the guard—nuclear pore complex quality control

“…More recently, the nuclear-vacuolar junction (NVJ), a vacuole-ONM contact site that is required for piecemeal microautophagy of the nucleus (PMN), has also been implicated in dealing with NPC misassembly stress triggered by NPC assembly mutants or by altering lipid metabolism [68]. Logical hypotheses are that PMN is required for ensuring a proper lipid balance that supports NPC assembly and/or for the clearance of defective NPC assembly structures [69]. The latter model is consistent with the observation that functional NPCs are excluded from the NVJ and are not targets of PMN [70,71], whereas some nups may be degraded by this pathway [68].…”