In selective autophagy of the nucleus (hereafter nucleophagy), nucleus-derived double-membrane vesicles (NDVs) are formed, sequestered within autophagosomes, and delivered to lysosomes or vacuoles for degradation. In Saccharomyces cerevisiae, the nuclear envelope (NE) protein Atg39 acts as a nucleophagy receptor, which interacts with Atg8 to target NDVs to the forming autophagosomal membranes. In this study, we revealed that Atg39 is anchored to the outer nuclear membrane via its transmembrane domain and also associated with the inner nuclear membrane via membrane-binding amphipathic helices (APHs) in its perinuclear space region, thereby linking these membranes. We also revealed that autophagosome formation-coupled Atg39 crowding causes the NE to protrude toward the cytoplasm, and the tips of the protrusions are pinched off to generate NDVs. The APHs of Atg39 are crucial for Atg39 crowding in the NE and subsequent NE protrusion. These findings suggest that the nucleophagy receptor Atg39 plays pivotal roles in NE deformation during the generation of NDVs to be degraded by nucleophagy.
Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus
K. Mochida’s present address is Laboratory for Protein Conformation Diseases, RIKEN Center for Brain Science, Wako, Japan.
- Award Id(s): JP17H01430,JP19H05708
- Award Id(s): JP21gm1410004
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Keisuke Mochida, Toshifumi Otani, Yuto Katsumata, Hiromi Kirisako, Chika Kakuta, Tetsuya Kotani, Hitoshi Nakatogawa; Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus. J Cell Biol 7 February 2022; 221 (2): e202103178. doi: https://doi.org/10.1083/jcb.202103178
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