bims-ershed 2023-07-09 papers

J Cell Mol Med. 2023 Jul 06.

Endoplasmic reticulum homeostasis-From molecules to organisms: Report on the 14th International Calreticulin Workshop, Saint Malo, France.

Ketsia Bakambamba, Federico Di Modugno, Marianne Guilbard, Simon Le Goupil, Stephanie Lhomond, Diana Pelizzari-Raymundo, Tony Avril, Eric Chevet, Frédéric Delom, Elodie Lafont.

The Calreticulin Workshop, initiated in 1994 by Marek Michalak in Banff (Alberta, Canada), was first organized to be an informal scientific meeting attended by researchers working on diverse biological questions related to functions associated with the endoplasmic reticulum (ER)-resident lectin-like chaperone and applied to a wide range of biological systems and models. Since then, this workshop has broadened the range of topics to cover all ER-related functions, has become international and has been held in Canada, Chile, Denmark, Italy, Switzerland, UK, USA, Greece and this year in France. Each conference, which is organized every other year (pending world-wide pandemic), generally attracts between 50 and 100 participants, including both early career researchers and international scientific leaders to favour discussions and exchanges. Over the years, the International Calreticulin Workshop has become an important gathering of the calreticulin and ER communities as a whole. The 14th International Calreticulin Workshop occurred from May 9-12 in St-Malo, Brittany, France, and has been highlighted by its rich scientific content and open-minded discussions held in a benevolent atmosphere. The 15th International Calreticulin Workshop will be organized in 2025 in Brussels, Belgium.

Keywords: AGR2; Calreticulin; ER stress; cancer; chemotherapy; degenerative diseases; endoplasmic reticulum; immune regulation; unfolded protein response

DOI: https://doi.org/10.1111/jcmm.17840

Cell Biosci. 2023 Jul 03. 13(1): 123

ER Ca2+ overload activates the IRE1α signaling and promotes cell survival.

Song Zhao, Haiping Feng, Dongfang Jiang, Keyan Yang, Si-Tong Wang, Yu-Xin Zhang, Yun Wang, Hongmei Liu, Caixia Guo, Tie-Shan Tang.

BACKGROUND: Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. Although Ca2+ depletion has been known to cause ER stress which in turn activates the unfolded protein response (UPR), how UPR sensors/transducers respond to excess Ca2+ when ER stores are overloaded remain largely unclear.
RESULTS: Here, we report for the first time that overloading of ER Ca2+ can directly sensitize the IRE1α-XBP1 axis. The overloaded ER Ca2+ in TMCO1-deficient cells can cause BiP dissociation from IRE1α, promote the dimerization and stability of the IRE1α protein, and boost IRE1α activation. Intriguingly, attenuation of the over-activated IRE1α-XBP1s signaling by a IRE1α inhibitor can cause a significant cell death in TMCO1-deficient cells.
CONCLUSIONS: Our data establish a causal link between excess Ca2+ in ER stores and the selective activation of IRE1α-XBP1 axis, underscoring an unexpected role of overload of ER Ca2+ in IRE1α activation and in preventing cell death.

Keywords: ER Ca2+ overload; ER stress; IRE1α; TMCO1

DOI: https://doi.org/10.1186/s13578-023-01062-y

Front Microbiol. 2023 ;14 1157146

Endoplasmic stress sensor Ire1 is involved in cytosolic/nuclear protein quality control in Pichia pastoris cells independent of HAC1.

Yasmin Nabilah Binti Mohd Fauzee, Yuki Yoshida, Yukio Kimata.

In eukaryotic species, dysfunction of the endoplasmic reticulum (ER), namely, ER stress, provokes a cytoprotective transcription program called the unfolded protein response (UPR). The UPR is triggered by transmembrane ER-stress sensors, including Ire1, which acts as an endoribonuclease to splice and mature the mRNA encoding the transcription factor Hac1 in many fungal species. Through analyses of the methylotrophic yeast Pichia pastoris (syn. Komagataella phaffii), we revealed a previously unknown function of Ire1. In P. pastoris cells, the IRE1 knockout mutation (ire1Δ) and HAC1 knockout mutation (hac1Δ) caused only partially overlapping gene expression changes. Protein aggregation and the heat shock response (HSR) were induced in ire1Δ cells but not in hac1Δ cells even under non-stress conditions. Moreover, Ire1 was further activated upon high-temperature culturing and conferred heat stress resistance to P. pastoris cells. Our findings cumulatively demonstrate an intriguing case in which the UPR machinery controls cytosolic protein folding status and the HSR, which is known to be activated upon the accumulation of unfolded proteins in the cytosol and/or nuclei.

Keywords: Pichia pastoris; endoplasmic reticulum; stress response; unfolded protein response; yeast

DOI: https://doi.org/10.3389/fmicb.2023.1157146