Transglutaminase Type 2 Regulates ER-Mitochondria Contact Sites by Interacting with GRP75

D'Eletto, M; Rossin, F; Occhigrossi, L; Farrace, M G; Faccenda, D; Desai, R; Marchi, S; Refolo, G; Falasca, L; Antonioli, M; Ciccosanti, F; Fimia, G M; Pinton, P; Campanella, M; Piacentini, M

Abstract

Transglutaminase type 2 (TG2) is a multifunctional enzyme that plays a key role in mitochondria homeostasis under stressful cellular conditions. TG2 interactome analysis reveals an enzyme interaction with GRP75 (glucose-regulated protein 75). GRP75 localizes in mitochondria-associated membranes (MAMs) and acts as a bridging molecule between the two organelles by assembling the IP3R-GRP75-VDAC complex, which is involved in the transport of Ca2+ from the endoplasmic reticulum (ER) to mitochondria. We demonstrate that the TG2 and GRP75 interaction occurs in MAMs. The absence of the TG2-GRP75 interaction leads to an increase of the interaction between IP3R-3 and GRP75; a decrease of the number of ER-mitochondria contact sites; an impairment of the ER-mitochondrial Ca2+ flux; and an altered profile of the MAM proteome. These findings indicate TG2 is a key regulatory element of the MAMs.

Citation

D'Eletto, M., Rossin, F., Occhigrossi, L., Farrace, M. G., Faccenda, D., Desai, R., …Piacentini, M. (2018). Transglutaminase Type 2 Regulates ER-Mitochondria Contact Sites by Interacting with GRP75. Cell Reports, 25(12), 3573-3581. https://doi.org/10.1016/j.celrep.2018.11.094

• Journal Article Type: Article
• Acceptance Date: Nov 27, 2018
• Publication Date: Dec 26, 2018
• Deposit Date: Jan 16, 2019
• Publicly Available Date: Nov 20, 2020
• Journal: Cell Reports
• Print ISSN: 2211-1247
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 12
• Pages: 3573-3581
• DOI: https://doi.org/10.1016/j.celrep.2018.11.094
• Public URL: https://rvc-repository.worktribe.com/output/1384913