Degradation of Blos1 mRNA by IRE1 repositions lysosomes and protects cells from stress

The Journal of Cell Biology
Donghwi BaeJulie Hollien

Abstract

Cells respond to stress in the ER by initiating the widely conserved unfolded protein response. Activation of the ER transmembrane nuclease IRE1 leads to the degradation of specific mRNAs, but how this pathway affects the ability of cells to recover from stress is not known. Here, we show that degradation of the mRNA encoding biogenesis of lysosome-related organelles 1 subunit 1 (Blos1) leads to the repositioning of late endosomes (LEs)/lysosomes to the microtubule-organizing center in response to stress in mouse cells. Overriding Blos1 degradation led to ER stress sensitivity and the accumulation of ubiquitinated protein aggregates, whose efficient degradation required their independent trafficking to the cell center and the LE-associated endosomal sorting complexes required for transport. We propose that Blos1 regulation by IRE1 promotes LE-mediated microautophagy of protein aggregates and protects cells from their cytotoxic effects.

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Citations

Nov 15, 2019·F1000Research·G Elif KaragözDiego Acosta-Alvear
Sep 11, 2020·Journal of Cell Science·Sebastian Schuck
Jul 22, 2020·Nature Chemical Biology·Julia M D GrandjeanR Luke Wiseman
Apr 22, 2020·Cellular and Molecular Life Sciences : CMLS·Celso Almeida, Margarida D Amaral
Sep 6, 2020·The Journal of Biological Chemistry·Julia M D Grandjean, R Luke Wiseman
Jul 1, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Kaiyuan WuMichael N Sack
Jul 20, 2019·Bio-protocol·G Elif KaragözDiego Acosta-Alvear
Mar 23, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Koffi L LakpaJonathan D Geiger
Oct 11, 2020·Trends in Cell Biology·Matías González-QuirozRémy Pedeux
Dec 17, 2021·Nature Communications·Adrien Le ThomasAvi Ashkenazi
Jul 19, 2019··Diego Acosta-AlvearG. Karagöz

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Methods Mentioned

BETA
protein folding
GTPase
PCR

Software Mentioned

ImageJ

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