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

Autor: Coppin L; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France., Jannin A; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France., Ait Yahya E; CHU Lille, Institut de Biochimie & Biologie Moléculaire, Centre de Biologie et Pathologie, F-59000, Lille, France., Thuillier C; CHU Lille, Institut de Génétique, Centre de Biologie et Pathologie, F-59000, Lille, France., Villenet C; University of Lille, CHU Lille, Plate-forme de génomique fonctionnelle, Centre de Biologie et Pathologie, F-59000, Lille, France., Tardivel M; University of Lille, F-59000, Lille, France., Bongiovanni A; University of Lille, F-59000, Lille, France., Gaston C; Equipe Cell adhesion and mechanics, Institut Jacques Monod - UMR 7592 CNRS - Université Paris Diderot, F-75205, Paris Cedex 13, France., de Beco S; Equipe Cell adhesion and mechanics, Institut Jacques Monod - UMR 7592 CNRS - Université Paris Diderot, F-75205, Paris Cedex 13, France., Barois N; University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France., van Seuningen I; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France., Durand E; University of Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199, EGID, F-59000, Lille, France., Bonnefond A; University of Lille, CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199, EGID, F-59000, Lille, France., Vienne JC; CHU Lille, Institut de Biochimie & Biologie Moléculaire, Centre de Biologie et Pathologie, F-59000, Lille, France., Vamecq J; CHU Lille, Institut de Biochimie & Biologie Moléculaire, Centre de Biologie et Pathologie, F-59000, Lille, France., Figeac M; University of Lille, CHU Lille, Plate-forme de génomique fonctionnelle, Centre de Biologie et Pathologie, F-59000, Lille, France., Vincent A; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France., Delacour D; Equipe Cell adhesion and mechanics, Institut Jacques Monod - UMR 7592 CNRS - Université Paris Diderot, F-75205, Paris Cedex 13, France., Porchet N; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France., Pigny P; University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR-S 1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France. pascal.pigny@inserm.fr.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2020 May 12; Vol. 11 (5), pp. 360. Date of Electronic Publication: 2020 May 12.
DOI: 10.1038/s41419-020-2556-3
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: