Abstract
MAMs, the physical association between the Endoplasmic Reticulum (ER) and mitochondria are, functional domains performing a significant role in the maintenance of cellular homeostasis. It is evolving as an important signaling center that coordinates nutrient and hormonal signaling for the proper regulation of hepatic insulin action and glucose homeostasis. Moreover, MAMs can be considered as hot spots for the transmission of stress signals from ER to mitochondria. The altered interaction between ER and mitochondria results in the amendment of several insulin-sensitive tissues, revealing the role of MAMs in glucose homeostasis. The development of mitochondrial dysfunction, ER stress, altered lipid and Ca2+ homeostasis are typically co-related with insulin resistance and β cell dysfunction. But little facts are known about the role played by these stresses in the development of metabolic disorders. In this review, we highlight the mechanisms involved in maintaining the contact site with new avenues of investigations for the development of novel preventive and therapeutic targets for T2DM.
Keywords: Mitochondria associated membranes, endoplasmic reticulum, mitochondria, calcium ions, insulin resistance, T2DM.
[http://dx.doi.org/10.1038/nature05482] [PMID: 17167471]
[http://dx.doi.org/10.1006/scdb.2000.0172] [PMID: 10966857]
[http://dx.doi.org/10.1038/nm1259] [PMID: 15980866]
[http://dx.doi.org/10.1038/nrm829] [PMID: 12042763]
[http://dx.doi.org/10.1038/sj.emboj.7601974] [PMID: 18216874]
[http://dx.doi.org/10.1172/JCI29103] [PMID: 16823478]
[http://dx.doi.org/10.1007/s001250051130] [PMID: 10064091]
[http://dx.doi.org/10.1210/en.2004-0478] [PMID: 15297438]
[http://dx.doi.org/10.1172/JCI420] [PMID: 9486980]
[http://dx.doi.org/10.1172/JCI117042] [PMID: 8113418]
[http://dx.doi.org/10.1073/pnas.91.23.10878] [PMID: 7971976]
[http://dx.doi.org/10.1074/jbc.M010286200] [PMID: 11278654]
[http://dx.doi.org/10.1016/j.molmet.2014.05.004] [PMID: 25061559]
[http://dx.doi.org/10.1007/s11010-011-1211-9] [PMID: 22246806]
[http://dx.doi.org/10.1016/j.lfs.2010.10.012] [PMID: 20970436]
[http://dx.doi.org/10.1016/j.nutres.2015.05.006] [PMID: 26055348]
[http://dx.doi.org/10.1111/hepr.12551] [PMID: 26147696]
[http://dx.doi.org/10.1038/cddis.2014.162] [PMID: 24743734]
[http://dx.doi.org/10.1210/er.2007-0023] [PMID: 18048763]
[http://dx.doi.org/10.1074/jbc.R400019200] [PMID: 15258147]
[http://dx.doi.org/10.1016/j.coph.2006.09.002] [PMID: 17045527]
[http://dx.doi.org/10.2337/diab.46.11.1733] [PMID: 9356019]
[http://dx.doi.org/10.1073/pnas.0809677105] [PMID: 19011102]
[http://dx.doi.org/10.1016/j.molcel.2004.08.025] [PMID: 15350220]
[http://dx.doi.org/10.1083/jcb.200311055] [PMID: 14757749]
[http://dx.doi.org/10.1111/j.1463-1326.2010.01281.x] [PMID: 21029306]
[http://dx.doi.org/10.1016/S0959-440X(98)80037-7] [PMID: 9631292]
[http://dx.doi.org/10.1007/s11892-014-0492-2] [PMID: 24740729]
[http://dx.doi.org/10.1016/j.mce.2008.03.004] [PMID: 18485584]
[http://dx.doi.org/10.1111/j.1463-1326.2009.01112.x] [PMID: 19817790]
[http://dx.doi.org/10.1038/nrm2199] [PMID: 17565364]
[http://dx.doi.org/10.1038/35014014] [PMID: 10854322]
[http://dx.doi.org/10.1038/sj.cdd.4401840] [PMID: 16397578]
[http://dx.doi.org/10.1101/gad.12.12.1812] [PMID: 9637683]
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00666.x] [PMID: 8670804]
[http://dx.doi.org/10.1074/jbc.271.30.18181] [PMID: 8663458]
[http://dx.doi.org/10.1038/415092a] [PMID: 11780124]
[http://dx.doi.org/10.1016/S0092-8674(01)00611-0] [PMID: 11779464]
[http://dx.doi.org/10.1016/S1097-2765(00)80251-8] [PMID: 10882108]
[http://dx.doi.org/10.1128/MCB.23.21.7448-7459.2003] [PMID: 14559994]
[http://dx.doi.org/10.1016/j.molcel.2007.06.011] [PMID: 17612490]
[http://dx.doi.org/10.1371/journal.pbio.1002277] [PMID: 26469762]
[http://dx.doi.org/10.1126/science.287.5453.664] [PMID: 10650002]
[http://dx.doi.org/10.1101/gad.992302] [PMID: 12050113]
[http://dx.doi.org/10.1042/bj3550019] [PMID: 11256944]
[PMID: 17765679]
[http://dx.doi.org/10.1016/j.devcel.2007.07.018] [PMID: 17765680]
[http://dx.doi.org/10.1089/ars.2007.1764] [PMID: 17760508]
[http://dx.doi.org/10.1101/cshperspect.a013169] [PMID: 23388626]
[http://dx.doi.org/10.1016/j.biocel.2007.01.020] [PMID: 17466566]
[http://dx.doi.org/10.1016/S1097-2765(03)00105-9] [PMID: 12667446]
[http://dx.doi.org/10.1084/jem.20071460] [PMID: 18458112]
[http://dx.doi.org/10.1038/nprot.2009.151] [PMID: 19816421]
[http://dx.doi.org/10.1038/srep27351] [PMID: 27272971]
[http://dx.doi.org/10.1016/j.coph.2016.03.002] [PMID: 27043073]
[http://dx.doi.org/10.1016/j.celrep.2016.07.082] [PMID: 27545895]
[http://dx.doi.org/10.4161/23723548.2014.956469] [PMID: 27308328]
[http://dx.doi.org/10.1016/j.biocel.2014.01.019] [PMID: 24534274]
[http://dx.doi.org/10.1016/j.bbabio.2013.10.015] [PMID: 24211533]
[http://dx.doi.org/10.1016/j.cmet.2014.01.010] [PMID: 24561263]
[http://dx.doi.org/10.1016/j.tcb.2007.07.010] [PMID: 17825565]
[http://dx.doi.org/10.1016/j.bbalip.2013.11.014] [PMID: 24316057]
[http://dx.doi.org/10.1038/nrm3440] [PMID: 22992592]
[http://dx.doi.org/10.1038/nature07534] [PMID: 19052620]
[http://dx.doi.org/10.1016/j.molcel.2013.04.023] [PMID: 23727017]
[http://dx.doi.org/10.1083/jcb.200608073] [PMID: 17178908]
[http://dx.doi.org/10.1016/j.bbamcr.2014.05.011] [PMID: 24875902]
[http://dx.doi.org/10.1016/j.cmet.2006.03.007] [PMID: 16679290]
[http://dx.doi.org/10.1038/nature09968] [PMID: 21532591]
[http://dx.doi.org/10.1124/mol.109.062539] [PMID: 20053954]
[http://dx.doi.org/10.1016/j.tem.2016.09.002] [PMID: 27670636]
[http://dx.doi.org/10.1038/nrm3412] [PMID: 22850819]
[http://dx.doi.org/10.1007/s10863-016-9672-x] [PMID: 27497945]
[http://dx.doi.org/10.1016/j.molcel.2016.05.040] [PMID: 27397688]
[http://dx.doi.org/10.1038/onc.2016.31] [PMID: 26973249]
[http://dx.doi.org/10.1016/j.cell.2011.11.022] [PMID: 22153070]
[http://dx.doi.org/10.1111/eci.12135] [PMID: 23869410]
[http://dx.doi.org/10.1007/s00424-012-1122-y] [PMID: 22706634]
[http://dx.doi.org/10.1073/pnas.0808953105] [PMID: 19098100]
[http://dx.doi.org/10.1523/JNEUROSCI.3159-11.2011] [PMID: 22049414]
[http://dx.doi.org/10.1093/bioinformatics/btq326] [PMID: 20554689]
[http://dx.doi.org/10.1016/j.cell.2010.06.007] [PMID: 20655468]
[http://dx.doi.org/10.1016/j.bbabio.2009.05.011] [PMID: 19481532]
[http://dx.doi.org/10.1016/j.ceca.2012.03.003] [PMID: 22502861]
[http://dx.doi.org/10.1152/ajpcell.2000.278.2.C423] [PMID: 10666039]
[http://dx.doi.org/10.2337/db13-1751] [PMID: 24947355]
[http://dx.doi.org/10.1186/PREACCEPT-1950166084128344] [PMID: 25376904]
[http://dx.doi.org/10.1152/ajpendo.00146.2013] [PMID: 24085037]
[http://dx.doi.org/10.1016/j.bbrc.2008.07.153] [PMID: 18723000]
[http://dx.doi.org/10.1126/science.1189157] [PMID: 21030605]
[http://dx.doi.org/10.1016/j.bbrc.2011.08.034] [PMID: 21867682]
[http://dx.doi.org/10.1073/pnas.261702698] [PMID: 11930000]
[http://dx.doi.org/10.1128/MCB.25.3.1135-1145.2005] [PMID: 15657439]
[http://dx.doi.org/10.1038/cdd.2013.77] [PMID: 23811847]
[http://dx.doi.org/10.1073/pnas.0711324105] [PMID: 18250332]
[http://dx.doi.org/10.1038/cdd.2015.101] [PMID: 26206086]
[http://dx.doi.org/10.2337/db17-0316] [PMID: 29326365]
[http://dx.doi.org/10.1093/jmcb/mjw004] [PMID: 26892023]
[http://dx.doi.org/10.1038/cr.2013.159] [PMID: 24296784]
[http://dx.doi.org/10.1038/nature11910] [PMID: 23455425]
[http://dx.doi.org/10.1016/j.cub.2016.12.038] [PMID: 28132811]
[http://dx.doi.org/10.1080/15548627.2015.1017191] [PMID: 25715028]
[http://dx.doi.org/10.1080/15548627.2016.1277309] [PMID: 28368777]
[http://dx.doi.org/10.15252/embj.201593102] [PMID: 27145933]
[http://dx.doi.org/10.1038/ni.2237] [PMID: 22430786]
[http://dx.doi.org/10.1073/pnas.1100255108] [PMID: 21876127]
[http://dx.doi.org/10.1523/JNEUROSCI.2507-13.2014] [PMID: 24381286]
[http://dx.doi.org/10.1016/j.biocel.2011.10.012] [PMID: 22064245]
[http://dx.doi.org/10.1172/JCI4431] [PMID: 9884331]
[http://dx.doi.org/10.1074/jbc.M112.349142] [PMID: 22619170]
[http://dx.doi.org/10.1371/journal.pone.0076941] [PMID: 24204710]
[http://dx.doi.org/10.1242/jcs.080762] [PMID: 21628424]
[http://dx.doi.org/10.1074/jbc.M112.359174] [PMID: 22511781]
[http://dx.doi.org/10.1073/pnas.1108220109] [PMID: 22427360]
[http://dx.doi.org/10.1073/pnas.1110133108] [PMID: 21844353]
[http://dx.doi.org/10.1073/pnas.1606786113] [PMID: 27647893]
[http://dx.doi.org/10.1101/cshperspect.a025817] [PMID: 28461574]
[http://dx.doi.org/10.15252/embr.201541108] [PMID: 27113756]
[http://dx.doi.org/10.1074/jbc.M109.056960] [PMID: 20042613]
[http://dx.doi.org/10.1089/ars.2011.4004] [PMID: 21854214]
[http://dx.doi.org/10.14348/molcells.2018.0438] [PMID: 30590907]
[http://dx.doi.org/10.1177/0269881110376692] [PMID: 20817751]
[http://dx.doi.org/10.1016/j.coph.2008.01.005] [PMID: 18313359]
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[http://dx.doi.org/10.1038/sj.emboj.7600559] [PMID: 15692567]
[http://dx.doi.org/10.1016/j.tips.2016.01.003] [PMID: 26869505]
[http://dx.doi.org/10.1016/j.cell.2005.08.012] [PMID: 16125763]
[http://dx.doi.org/10.1038/s41419-017-0025-4] [PMID: 29491402]
[http://dx.doi.org/10.1016/j.bbamcr.2016.12.024] [PMID: 28064002]
[http://dx.doi.org/10.1371/journal.pone.0182027] [PMID: 28742858]
[http://dx.doi.org/10.1016/j.cellsig.2008.10.004] [PMID: 18950706]
[http://dx.doi.org/10.1007/s00125-015-3829-8] [PMID: 26660890]
[http://dx.doi.org/10.1016/j.cmet.2012.03.015] [PMID: 22521878]
[http://dx.doi.org/10.3748/wjg.v19.i10.1572] [PMID: 23538485]
[http://dx.doi.org/10.1093/hmg/ddu193] [PMID: 24833725]
[http://dx.doi.org/10.1038/nm.3735] [PMID: 25419710]
[http://dx.doi.org/10.1016/j.cell.2013.09.003] [PMID: 24074867]
[http://dx.doi.org/10.1242/jcs.093609] [PMID: 23843617]
[http://dx.doi.org/10.1167/iovs.16-19232] [PMID: 27701635]
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.06.042] [PMID: 22781655]
[http://dx.doi.org/10.1038/s41598-017-02213-1] [PMID: 28522876]
[http://dx.doi.org/10.1002/dmrr.2584] [PMID: 25069700]