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bioRxiv · 10.1101/2021.03.29.437603

Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus

Mochida, K.·Otani, T.·Katsumata, Y.·Kirisako, H.·Kakuta, C.·Kotani, T.·Nakatogawa, H.
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Abstract

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 forming autophagosomal membranes. In this study, we revealed that Atg39 is anchored to the outer nuclear membrane (ONM) via its transmembrane domain and also associated with the inner nuclear membrane (INM) via membrane-binding amphipathic helices (APHs) in its perinuclear space region, thereby linking these membranes. We also revealed that overaccumulation of Atg39 causes the NE to protrude towards the cytoplasm, and the tips of the protrusions are pinched off to generate NDVs. The APHs of Atg39 are crucial for Atg39 assembly 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.

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Mochida, K., Otani, T., Katsumata, Y., Kirisako, H., Kakuta, C., Kotani, T., Nakatogawa, H.. 2021-03-29. Atg39 links and deforms the outer and inner nuclear membranes in selective autophagy of the nucleus. https://doi.org/10.1101/2021.03.29.437603

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