Nuclear envelope-vacuole contacts mitigate nuclear pore complex assembly stress.

Area of Science:

• Cell Biology
• Molecular Biology
• Yeast Genetics

Background:

• Nuclear pore complex (NPC) biogenesis is crucial for nuclear transport and nuclear envelope (NE) morphology.
• Failures in NPC assembly can lead to cellular defects, but mechanisms for alleviating this stress are poorly understood.

Purpose of the Study:

• To investigate cellular mechanisms that mitigate stress during NPC assembly in Saccharomyces cerevisiae.
• To elucidate the role of nucleus-vacuole junctions (NVJs) in response to compromised NPC biogenesis.

Main Methods:

• Analysis of nup mutants in Saccharomyces cerevisiae.
• Investigating the role of NVJs and lipid droplets in NPC assembly.
• Studying the function of ATG1 in NE remodeling and nucleoporin degradation.

Main Results:

• NE-vacuole contacts (NVJs) increase in nup mutants with compromised NPC assembly.
• NVJs, along with lipid droplets, enhance NPC formation and cell viability in assembly mutants.
• NVJs cooperate with ATG1 to remodel the NE and promote vacuole-dependent degradation of nucleoporins.

Conclusions:

• NVJs play a critical role in mitigating cellular stress caused by disrupted NPC assembly.
• These interorganelle contacts significantly improve the physiology of NPC assembly mutants.
• The findings define a novel coordination mechanism between NE-vacuole contacts and cellular responses to maintain homeostasis.