Title :

Galectin-3 modulates epithelial cell adaptation to stress at the ER-mitochondria interface

Author(s) :

Coppin, Lucie [Auteur]
Jannin, Arnaud [Auteur]
Ait Yahya, Emilie [Auteur]
Thuillier, Caroline [Auteur]
Villenet, Céline [Auteur]
Tardivel, Meryem [Auteur]
Bongiovanni, Antonino [Auteur]
Gaston, Cécile [Auteur]
de Beco, Simon [Auteur]
Barois, Nicolas [Auteur]
Van Seuningen, Isabelle [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Durand, Emmanuelle [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Bonnefond, Amelie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Vienne, Jean-Claude [Auteur]
Vamecq, Joseph [Auteur]
Figeac, Martin [Auteur]
Vincent, Audrey [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Delacour, Delphine [Auteur]
Porchet, Nicole [Auteur]
Pigny, Pascal [Auteur]

Journal title :

Cell Death and Disease

Pages :

360

Publisher :

Nature Publishing Group

Publication date :

2020-05-12

ISSN :

2041-4889

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Abstract Cellular stress response contributes to epithelial defense in adaptation to environment changes. Galectins play a pivotal role in the regulation of this response in malignant cells. However, precise underlying ...
Show more >Abstract Cellular stress response contributes to epithelial defense in adaptation to environment changes. Galectins play a pivotal role in the regulation of this response in malignant cells. However, precise underlying mechanisms are largely unknown. Here we demonstrate that Galectin-3, a pro and anti-apoptotic lectin, is required for setting up a correct cellular response to stress by orchestrating several effects. First, Galectin-3 constitutes a key post-transcriptional regulator of stress-related mRNA regulons coordinating the cell metabolism, the mTORC1 complex or the unfolded protein response (UPR). Moreover, we demonstrated the presence of Galectin-3 with mitochondria-associated membranes (MAM), and its interaction with proteins located at the ER or mitochondrial membranes. There Galectin-3 prevents the activation and recruitment at the mitochondria of the regulator of mitochondria fission DRP-1. Accordingly, loss of Galectin-3 impairs mitochondrial morphology, with more fragmented and round mitochondria, and dynamics both in normal and cancer epithelial cells in basal conditions. Importantly, Galectin-3 deficient cells also display changes of the activity of the mitochondrial respiratory chain complexes, of the mTORC1/S6RP/4EBP1 translation pathway and reactive oxygen species levels. Regarding the ER, Galectin-3 did not modify the activities of the 3 branches of the UPR in basal conditions. However, Galectin-3 favours an adaptative UPR following ER stress induction by Thapsigargin treatment. Altogether, at the ER-mitochondria interface, Galectin-3 coordinates the functioning of the ER and mitochondria, preserves the integrity of mitochondrial network and modulates the ER stress response.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL