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A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function

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A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function International Journal of Environmental Research and Public Health Review A Review of the Role of Endo/Sarcoplasmic Reticulum-Mitochondria Ca2+ Transport in Diseases and Skeletal Muscle Function Shuang-Shuang Zhang 1,2, Shi Zhou 2 , Zachary J. Crowley-McHattan 2 , Rui-Yuan Wang 1,* and Jun-Ping Li 1 1 School of Sport Science, Beijing Sport University, Beijing 100084, China; [email protected] (S.-S.Z.); [email protected] (J.-P.L.) 2 Faculty of Health, Southern Cross University, East Lismore, NSW 2480, Australia; [email protected] (S.Z.); [email protected] (Z.J.C.-M.) * Correspondence: [email protected] Abstract: The physical contact site between a mitochondrion and endoplasmic reticulum (ER), named the mitochondria-associated membrane (MAM), has emerged as a fundamental platform for regulat- ing the functions of the two organelles and several cellular processes. This includes Ca2+ transport from the ER to mitochondria, mitochondrial dynamics, autophagy, apoptosis signalling, ER stress sig- nalling, redox reaction, and membrane structure maintenance. Consequently, the MAM is suggested to be involved in, and as a possible therapeutic target for, some common diseases and impairment in skeletal muscle function, such as insulin resistance and diabetes, obesity, neurodegenerative diseases, Duchenne muscular dystrophy, age-related muscle atrophy, and exercise-induced muscle damage. Citation: Zhang, S.-S.; Zhou, S.; In the past decade, evidence suggests that alterations in Ca2+ transport from the ER to mitochondria, Crowley-McHattan, Z.J.; Wang, R.-Y.; mediated by the macromolecular complex formed by IP3R, Grp75, and VDAC1, may be a universal Li, J.-P. A Review of the Role of mechanism for how ER-mitochondria cross-talk is involved in different physiological/pathological Endo/Sarcoplasmic conditions mentioned above. A better understanding of the ER (or sarcoplasmic reticulum in muscle)- Reticulum-Mitochondria Ca2+ mitochondria Ca2+ transport system may provide a new perspective for exploring the mechanism of Transport in Diseases and Skeletal Muscle Function. Int. J. Environ. Res. how the MAM is involved in the pathology of diseases and skeletal muscle dysfunction. This review Public Health 2021, 18, 3874. provides a summary of recent research findings in this area. https://doi.org/10.3390/ 2+ ijerph18083874 Keywords: mitochondria-associated membrane; endo/sarcoplasmic reticulum-mitochondria Ca transport; mitochondrial calcium overload; skeletal muscle function Academic Editor: Paul B. Tchounwou Received: 21 February 2021 Accepted: 24 March 2021 1. Introduction Published: 7 April 2021 Mitochondria and endoplasmic reticulum (ER) are two organelles in a cell that play essential roles in cellular survival and stress responses. The mitochondrion is the power- Publisher’s Note: MDPI stays neutral house of the cell. The ER is involved in protein synthesis, modification, secretion, lipid and with regard to jurisdictional claims in steroid synthesis, and modulation of Ca2+ signalling. Sarcoplasmic reticulum (SR) is a published maps and institutional affil- special form of ER in striated muscle; it is specialised in the lipid synthesis, Ca2+ mod- iations. ulation, and excitation–contraction coupling. Structurally and functionally, these two organelles are connected via the mitochondria-associated membrane (MAM), a contact site that acts as a platform for inter-organelle communication [1]. In particular, the MAM is involved in a multitude of cellular processes [2], among which the Ca2+ transport Copyright: © 2021 by the authors. from the ER to the mitochondrion (ER-mitochondria Ca2+ transport) is the focus of this Licensee MDPI, Basel, Switzerland. review. This process is mediated by the molecular complex inositol 1,4,5-triphosphate This article is an open access article receptor (IP3R)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel distributed under the terms and 1 (VDAC1), which works as a hub for cellular survival and death based on its role in conditions of the Creative Commons regulating mitochondrial physiology and cellular Ca2+ homeostasis [3,4]. During the past Attribution (CC BY) license (https:// decade, alterations of ER-mitochondria Ca2+ transport have been observed in diabetes, creativecommons.org/licenses/by/ 4.0/). obesity, cancer, neurodegenerative diseases like Alzheimer’s disease and Parkinson’s dis- Int. J. Environ. Res. Public Health 2021, 18, 3874. https://doi.org/10.3390/ijerph18083874 https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2021, 18, 3874 2 of 12 Int. J. Environ. Res. Public Health 2021, 18, x 2 of 13 ease, and ischemia/reperfusion injuries in which the integrity or number of MAMs are changed [2,5]. obesity, cancer, neurodegenerative diseases like Alzheimer’s disease and Parkinson’s Skeletal muscle is a high energy-consuming organ in which adequate energy supply disease, and ischemia/reperfusion injuries in which the integrity or number of 2+MAMs are cishanged essential [2,5]. for muscle performance. Changes in mitochondrial Ca homeostasis could 2+ causeSkeletal Ca -dependentmuscle is a high damage energy- toconsuming mitochondrial organ in structurewhich adequate and function.energy supply Conjecture ex- isists essential that these for muscle changes performance. contribute Changes to the in age- mitochondrial and disease-related Ca2+ homeostasis attenuation could in muscle causeperformance Ca2+-dependent [6]. There damage are to alsomitochondrial some indications structure and that function. these changesConjecture may exists contribute to thatexercise-induced these changes contribute muscle damage to the age [7–-9 ].and The disease [Ca2+-related] variations attenuation on eitherin muscle the outer mito- performance [6]. There are also some indications that these changes may contribute2+ to chondrial membrane (OMM) surface or within mitochondria ([Ca ]mt), in response to exercise-induced muscle damage [7–9]. The [Ca2+] variations on either the2+ outer stimulation of the IP3R, are frequently measured for exploring the Ca communication mitochondrial membrane (OMM) surface or within mitochondria ([Ca2+]mt), in response between the ER and mitochondria in the liver and brain [10–12]. However, few studies to stimulation of the IP3R, are frequently measured for exploring the Ca2+ communication betweenhave been the ER undertaken and mitochondria on skeletal in the muscleliver and in brain this [10 regard.–12]. However, The MAM’s few studies role concerning haveimpaired been undertaken skeletal muscle on skeletal function muscle has in beenthis regard. confirmed The MAM’s in muscular role concerning dystrophy, ageing, impairedand insulin skeletal resistance, muscle function with the has evidence been confirmed that there in muscular is a reduction dystrophy, in ageing, the number and of MAMs insulinin these resistance, conditions with [ 13the– evidence15]. A reduced that there MAM is a reduction number in has the alsonumber been of implicatedMAMs in in heavy- theseload conditions endurance [13 exercise–15]. A reduced that may MAM be number caused has by also SR stressbeen implicated and an increased in heavy-load mitochondrial endurancedivision rateexercise [16– 18that]. Furthermore,may be caused accordingby SR stress to and the an studies increased investigating mitochondrial MAM and ER- divisionmitochondria rate [16– Ca18].2+ Furthermore,transport in according response to tothe ER studies stress investigating [13], mitochondrial MAM and ER dynamics- [19], mitochondria Ca2+ transport in response to ER stress [13], mitochondrial dynamics [19], and insulin resistance [20], speculation has arisen that this transport system plays an and insulin resistance [20], speculation2+ has arisen that this transport system plays an essentialessential role role in inmitochondrial mitochondrial Ca2+ overload Ca overload in response in response to intensive to e intensivexercise (Figure exercise 1). (Figure1). Figure 1. The changes in ER/SR-mitochondrial Ca2+ transport2+ mediated by IP3R-Grp75-VDAC1 that Figure 1. The changes in ER/SR-mitochondrial Ca transport mediated by IP3R-Grp75-VDAC1 are involved in diseases and skeletal muscle dysfunction. Under normal physiological conditions, that are involved in diseases and skeletal muscle dysfunction. Under normal physiological condi- parts of the mitochondrial membrane are physically connected to the ER/SR. The ER/SR- mitochondriations, parts Ca of2+ the transport mitochondrial is mediated membrane by the macromolecular are physically complex connected IP3R-Grp75 to- theVDAC1 ER/SR. and The ER/SR- 2+ 2+ suppliesmitochondria Ca to Camitochondriatransport for isATP mediated production. by the However, macromolecular an increase complexin ER/SR-mitochondria IP3R-Grp75-VDAC1 and supplies Ca2+ to mitochondria for ATP production. However, an increase in ER/SR-mitochondria Ca2+ transport is involved in diseases such as Alzheimer’s disease, hepatic diabetes, heart is- chemia/reperfusion injury, and skeletal muscle impairment. A decrease in the ER/SR-mitochondria Ca2+ transport is also a contributing factor for Parkinson’s disease, insulin resistance in the liver, and muscle performance reduction. Int. J. Environ. Res. Public Health 2021, 18, 3874 3 of 12 The aims of this review are (1) to summarise the current literature on the function of the MAM and Ca2+ transport from the ER (or SR) to mitochondria, mediated by the 2+ IP3R-Grp75-VDAC1 complex, in regulating mitochondrial Ca homeostasis; and (2) to discuss the changes in
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