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

First Author  D'Eletto M Year  2018
Journal  Cell Rep Volume  25
Issue  13 Pages  3573-3581.e4
PubMed ID  30590033 Mgi Jnum  J:271639
Mgi Id  MGI:6279063 Doi  10.1016/j.celrep.2018.11.094
Citation  D'Eletto M, et al. (2018) Transglutaminase Type 2 Regulates ER-Mitochondria Contact Sites by Interacting with GRP75. Cell Rep 25(13):3573-3581.e4
abstractText  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 Ca(2+) 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 Ca(2+) flux; and an altered profile of the MAM proteome. These findings indicate TG2 is a key regulatory element of the MAMs.
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