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

Authors :
Manuela D’Eletto
Federica Rossin
Luca Occhigrossi
Maria Grazia Farrace
Danilo Faccenda
Radha Desai
Saverio Marchi
Giulia Refolo
Laura Falasca
Manuela Antonioli
Fabiola Ciccosanti
Gian Maria Fimia
Paolo Pinton
Michelangelo Campanella
Mauro Piacentini
Source :
Cell Reports, Vol 25, Iss 13, Pp 3573-3581.e4 (2018)
Publication Year :
2018
Publisher :
Elsevier, 2018.

Abstract

Summary: 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. : TG2 is an enzyme that plays a key role in mitochondria homeostasis. D’eletto et al. found that TG2 interacts with GRP75, a protein localized in mitochondria-associated membranes (MAMs). TG2 regulates the number of ER-mitochondria contact sites and Ca2+ flux, suggesting a key regulatory role in MAMs. Keywords: mitochondrial Ca2+, MAMs, GRP75, TG2, ER-mitochondria contact sites

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
25
Issue :
13
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.83291863d9942ff9278c205e58a4ea1
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2018.11.094