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

Abstract

Highlights d TG2 interacts with GRP75 in mitochondria-associated membranes (MAMs) d TG2 influences the number of ER-mitochondria contact sites d TG2 regulates the interaction between IP3R3 and GRP75 d TG2 controls ER-mitochondrial Ca 2+ flux and protein expression in MAMs

ER–Mitochondria Contact Sites Reporters: Strengths and Weaknesses of the Available Approaches

“…As reported in the second paragraph, the ER-mitochondria tethering is characterized by four main players, IP3R-GRP75-VDAC [39], BAP31-FIS1 [36], Mfn2 [28], and VAP-PTPIP51 [32]. However, to date, more proteins have been reported to be resident at MAMs [118,119]. Indeed, although cell fractionation and EM are the primary and mostly commonly used techniques amenable to discover and investigate ER-mitochondria tethering [39,120], BAP31-FIS1 [36], VAP-PTPIP51 [32], a deeper investigation has been reached in terms of the development of ameliorate approaches.…”

Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update

“…This evidence confirms that only little is known about this channel, particularly in cardiac and vascular homeostasis or metabolism. The recent findings of the physical link between ER and mitochondria, mediated by a protein complex including ITPR, suggest a potential role of the receptor in the regulation of calcium-dependent mitochondrial metabolism [118][119][120][121][122][123][124][125][126][127][128][129][130]. The ability of ITPR to indirectly regulate mitochondrial energetic metabolism could have a significant impact on the health and homeostasis of the tissues strongly dependent on mitochondrial energetic production, such as cardiac and skeletal muscle.…”

Mitochondria-Associated ER Membranes – The Origin Site of Autophagy

“…In addition to the above, mass spectrometric analysis of MAMs proteins has been performed by several laboratories ( Zahedi et al, 2006 ; Poston et al, 2013 ; Ma et al, 2017 ; Wang et al, 2018 ). Since the MAMs are the signal communication platform, it mainly relies on proteins to perform its various functions, and the proteins located in MAMs are grouped according to their primary functions, for instance, Ca 2+ transport: inositol 1,4,5-triphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC1) ( Tubbs et al, 2014 ; D’Eletto et al, 2018 ); lipid metabolism: acyl coenzyme A-cholesterol acyltransferase (ACAT) ( Rusinol et al, 1994 ), acyl CoA:diacylgycerol acyltransferase 2 (DGAT2) ( Stone et al, 2009 ); autophagy: autophagy related 14 (ATG14), autophagy related 5 (ATG5) ( Hamasaki et al, 2013 ); and insulin signaling: protein kinase B (PKB), mammalian target of rapamycin complex (mTORC) ( Betz et al, 2013 ; Rieusset, 2017 ). These multifunctional protein groups also suggest that the MAM play an important role in maintaining intracellular homeostasis and biological functions.…”