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., Marchi, S., Refolo, G., Falasca, L., Antonioli, M., Ciccosanti, F., Fimia, G. M., Pinton, P., Campanella, M., & 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: Jan 22, 2019
• 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