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- Title
Galectin-3 modulates epithelial cell adaptation to stress at the ER-mitochondria interface.
- Authors
Coppin, Lucie; Jannin, Arnaud; Ait Yahya, Emilie; Thuillier, Caroline; Villenet, Céline; Tardivel, Meryem; Bongiovanni, Antonino; Gaston, Cécile; de Beco, Simon; Barois, Nicolas; van Seuningen, Isabelle; Durand, Emmanuelle; Bonnefond, Amélie; Vienne, Jean-Claude; Vamecq, Joseph; Figeac, Martin; Vincent, Audrey; Delacour, Delphine; Porchet, Nicole; Pigny, Pascal
- 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.
- Publication
Cell Death & Disease, 2020, Vol 11, Issue 5, p1
- ISSN
2041-4889
- Publication type
Article
- DOI
10.1038/s41419-020-2556-3