Selective autophagy degrades nuclear pore complexes
Chia‐Wei Lee, Florian Wilfling, Paolo Ronchi, Matteo Allegretti, Shyamal Mosalaganti, Stefan Jentsch, Martin Beck, Boris Pfander
Abstract
Nuclear pore complexes (NPCs) are very large proteinaceous assemblies that consist of more than 500 individual proteins1,2. NPCs are essential for nucleocytoplasmic transport of different cellular components, and disruption of the integrity of NPCs has been linked to aging, cancer and neurodegenerative diseases3–7. However, the mechanism by which membrane-embedded NPCs are turned over is currently unknown. Here we show that, after nitrogen starvation or genetic interference with the architecture of NPCs, nucleoporins are rapidly degraded in the budding yeast Saccharomyces cerevisiae. We demonstrate that NPC turnover involves vacuolar proteases and the core autophagy machinery. Autophagic degradation is mediated by the cytoplasmically exposed Nup159, which serves as intrinsic cargo receptor and directly binds to the autophagy marker protein Atg8. Autophagic degradation of NPCs is therefore inducible, enabling the removal of individual NPCs from the nuclear envelope. Lee et al. show that, after nitrogen starvation and genetic interference with the architecture of nuclear pore complexes, nucleoporins are degraded by autophagy, constituting a quality-control step at the nuclear envelope.