TMX4-driven LINC Complex Disassembly and Asymmetric Autophagy of the Nuclear Envelope Upon Acute ER Stress

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jun 13

PMID 37311770

Authors

Marika K Kucinska

Juliette Fedry

Carmela Galli

Diego Morone

Andrea Raimondi

Tatiana Solda

Friedrich Forster

Maurizio Molinari

Affiliations

Soon will be listed here.

Abstract

The endoplasmic reticulum (ER) is an organelle of nucleated cells that produces proteins, lipids and oligosaccharides. ER volume and activity are increased upon induction of unfolded protein responses (UPR) and are reduced upon activation of ER-phagy programs. A specialized domain of the ER, the nuclear envelope (NE), protects the cell genome with two juxtaposed lipid bilayers, the inner and outer nuclear membranes (INM and ONM) separated by the perinuclear space (PNS). Here we report that expansion of the mammalian ER upon homeostatic perturbations results in TMX4 reductase-driven disassembly of the LINC complexes connecting INM and ONM and in ONM swelling. The physiologic distance between ONM and INM is restored, upon resolution of the ER stress, by asymmetric autophagy of the NE, which involves the LC3 lipidation machinery, the autophagy receptor SEC62 and the direct capture of ONM-derived vesicles by degradative LAMP1/RAB7-positive endolysosomes in a catabolic pathway mechanistically defined as micro-ONM-phagy.

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