TORC1 inactivation stimulates autophagy of nucleoporin and nuclear pore complexes

• Published in: The Journal of cell biology Vol. 219; no. 7
• Main Authors: Tomioka, Yui, Kotani, Tetsuya, Kirisako, Hiromi, Oikawa, Yu, Kimura, Yayoi, Hirano, Hisashi, Ohsumi, Yoshinori, Nakatogawa, Hitoshi
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06.07.2020
• Subjects: Autophagosomes - drug effects; Autophagosomes - metabolism; Autophagy - drug effects; Autophagy - genetics; Autophagy-Related Protein 8 Family - genetics; Autophagy-Related Protein 8 Family - metabolism; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Cell Death and Autophagy; Gene Expression Regulation, Fungal; Mechanistic Target of Rapamycin Complex 1 - antagonists & inhibitors; Mechanistic Target of Rapamycin Complex 1 - genetics; Mechanistic Target of Rapamycin Complex 1 - metabolism; Microscopy, Immunoelectron; Nuclear Pore - drug effects; Nuclear Pore - metabolism; Nuclear Pore - ultrastructure; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; Protein Binding; Protein Kinase Inhibitors - pharmacology; Proteolysis - drug effects; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - ultrastructure; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction; Sirolimus - pharmacology; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201910063

The mechanisms underlying turnover of the nuclear pore complex (NPC) and the component nucleoporins (Nups) are still poorly understood. In this study, we found that the budding yeast Saccharomyces cerevisiae triggers NPC degradation by autophagy upon the inactivation of Tor kinase complex 1. This degradation largely depends on the selective autophagy-specific factor Atg11 and the autophagy receptor-binding ability of Atg8, suggesting that the NPC is degraded via receptor-dependent selective autophagy. Immunoelectron microscopy revealed that NPCs embedded in nuclear envelope-derived double-membrane vesicles are sequestered within autophagosomes. At least two pathways are involved in NPC degradation: Atg39-dependent nucleophagy (selective autophagy of the nucleus) and a pathway involving an unknown receptor. In addition, we found the interaction between Nup159 and Atg8 via the Atg8-family interacting motif is important for degradation of this nucleoporin not assembled into the NPC. Thus, this study provides the first evidence for autophagic degradation of the NPC and Nups, which we term "NPC-phagy" and "nucleoporinophagy."