Abstract
Background: Cancer cachexia is a metabolic syndrome prevalent in the majority of the advanced cancers and is associated with complications such as anorexia, early satiety, weakness, anaemia, and edema, thereby reducing performance and impairing quality of life. Skeletal muscle wasting is a characteristic feature of cancer-cachexia and mitochondria is responsible for regulating total protein turnover in skeletal muscle tissue.
Methods: We carried out exhaustive search for cancer cachexia and role of mitochondria in the same in various databases. All the relevant articles were gathered and the pertinent information was extracted out and compiled which was further structured into different sub-sections.
Results: Various findings on the mitochondrial alterations in connection to its disturbed normal physiology in various models of cancer-cachexia have been recently reported, suggesting a significant role of the organelle in the pathogenesis of the complications involved in the disorder. It has also been reported that reduced mitochondrial oxidative capacity is due to reduced mitochondrial biogenesis as well as altered balance between fusion and fission protein activities. Moreover, autophagy in mitochondria (termed as mitophagy) is reported to play an important role in cancer cachexia.
Conclusion: The present review aims to put forth the changes occurring in mitochondria and hence explore possible targets which can be exploited in cancer-induced cachexia for treatment of such a debilitating condition.
Keywords: Uncoupled proteins, mega-mitochondria, fragmented mitochondria, mitofusin-2, dynamin related protein 1, mitophagy.
Graphical Abstract
[http://dx.doi.org/10.1080/01635589809514722] [PMID: 9919615]
[http://dx.doi.org/10.1207/S15327914NC3701_4] [PMID: 10965517]
[http://dx.doi.org/10.1186/1476-4598-2-36] [PMID: 14613583]
[http://dx.doi.org/10.1016/j.clnu.2008.06.013] [PMID: 18718696]
[http://dx.doi.org/10.1007/s00520-010-0972-0] [PMID: 20714754]
[http://dx.doi.org/10.1016/j.lfs.2016.11.033] [PMID: 27919820]
[http://dx.doi.org/10.1529/biophysj.108.136077] [PMID: 18689447]
[PMID: 2394698]
[http://dx.doi.org/10.1146/annurev.genet.39.110304.095751] [PMID: 16285865]
[http://dx.doi.org/10.1152/advan.00029.2004] [PMID: 15545342]
[http://dx.doi.org/10.1007/s11906-010-0157-8] [PMID: 20967516]
[http://dx.doi.org/10.2353/ajpath.2007.060505] [PMID: 17255328]
[http://dx.doi.org/10.1371/journal.pone.0002086] [PMID: 18461174]
[http://dx.doi.org/10.1038/emboj.2010.60] [PMID: 20400940]
[http://dx.doi.org/10.1186/2044-5040-2-14] [PMID: 22769563]
[PMID: 21069263]
[http://dx.doi.org/10.1097/MCO.0000000000000161] [PMID: 25783794]
[http://dx.doi.org/10.1016/j.bbalip.2014.03.004] [PMID: 24657703]
[http://dx.doi.org/10.1152/ajpregu.00300.2010] [PMID: 21148472]
[http://dx.doi.org/10.1038/nrm2275] [PMID: 17928812]
[http://dx.doi.org/10.1038/79936] [PMID: 11017079]
[http://dx.doi.org/10.1038/79944] [PMID: 11017080]
[http://dx.doi.org/10.1038/ng1341] [PMID: 15064763]
[http://dx.doi.org/10.1056/NEJMoa064436] [PMID: 17460227]
[http://dx.doi.org/10.1083/jcb.200211046] [PMID: 12527753]
[http://dx.doi.org/10.1242/jcs.01565] [PMID: 15572413]
[http://dx.doi.org/10.1002/jcp.20950] [PMID: 17167772]
[http://dx.doi.org/10.1016/j.semcdb.2015.11.005] [PMID: 26593326]
[http://dx.doi.org/10.3389/fphys.2015.00422] [PMID: 26793123]
[http://dx.doi.org/10.1126/science.1099793] [PMID: 15297672]
[http://dx.doi.org/10.1016/j.cell.2006.06.010] [PMID: 16814712]
[http://dx.doi.org/10.2741/4303] [PMID: 25553445]
[http://dx.doi.org/10.1016/j.cell.2006.06.025] [PMID: 16839885]
[http://dx.doi.org/10.1083/jcb.201107053] [PMID: 21987634]
[http://dx.doi.org/10.3389/fphys.2013.00207] [PMID: 23966947]
[http://dx.doi.org/10.1111/j.1582-4934.2002.tb00452.x] [PMID: 12611638]
[http://dx.doi.org/10.1152/ajpcell.00272.2006] [PMID: 16870828]
[http://dx.doi.org/10.1007/s10741-007-9072-8] [PMID: 18172761]
[http://dx.doi.org/10.1038/labinvest.2010.43] [PMID: 20157292]
[http://dx.doi.org/10.3892/ijo.2013.1998] [PMID: 23817738]
[http://dx.doi.org/10.1016/j.yexcr.2007.09.013] [PMID: 17964571]
[http://dx.doi.org/10.1016/j.bbagen.2012.11.009] [PMID: 23200745]
[http://dx.doi.org/10.1016/j.febslet.2004.05.066] [PMID: 15225634]
[http://dx.doi.org/10.1139/H09-049] [PMID: 19448711]
[http://dx.doi.org/10.1016/S0014-5793(03)00124-8] [PMID: 12633852]
[http://dx.doi.org/10.1016/j.ejcb.2007.04.002] [PMID: 17532093]
[http://dx.doi.org/10.3892/ol.2016.5191] [PMID: 27895764]
[http://dx.doi.org/10.1242/jcs.157321] [PMID: 25271058]
[http://dx.doi.org/10.1126/science.1219855] [PMID: 22936770]
[http://dx.doi.org/10.1111/j.1742-4658.2011.08010.x] [PMID: 21232014]
[http://dx.doi.org/10.1113/expphysiol.2014.082255] [PMID: 25261498]
[http://dx.doi.org/10.1172/JCI34006] [PMID: 18246195]
[http://dx.doi.org/10.1093/hmg/ddn355] [PMID: 18945718s]
[http://dx.doi.org/10.1126/science.1104343] [PMID: 15662004]
[http://dx.doi.org/10.1042/bst0040399] [PMID: 137147]
[http://dx.doi.org/10.1042/bst0290751] [PMID: 11709069]
[http://dx.doi.org/10.1016/S0014-5793(98)01178-8] [PMID: 9801160]
[http://dx.doi.org/10.1016/j.febslet.2004.12.050] [PMID: 15670834]
[http://dx.doi.org/10.1093/qjmed/hci127] [PMID: 16214835]
[http://dx.doi.org/10.1038/sj.bjc.6603360] [PMID: 17047651]
[http://dx.doi.org/10.4161/15384047.2014.987075] [PMID: 25457061]
[http://dx.doi.org/10.1007/s13539-012-0071-9] [PMID: 22648737]
[http://dx.doi.org/10.1038/nature13528] [PMID: 25043053]
[http://dx.doi.org/10.1016/j.cmet.2014.06.011] [PMID: 25043816]
[http://dx.doi.org/10.1016/j.cmet.2014.07.005] [PMID: 25127354]
[http://dx.doi.org/10.1101/gad.276733.115] [PMID: 26944676]
[http://dx.doi.org/10.1002/jcb.10601] [PMID: 12938166]
[http://dx.doi.org/10.1007/s13539-012-0087-1] [PMID: 23097000]
[http://dx.doi.org/10.2174/157339906777950660] [PMID: 18220632]
[http://dx.doi.org/10.1038/cdd.2009.118] [PMID: 19696789]
[http://dx.doi.org/10.1124/mi.5.2.7] [PMID: 15821158]
[http://dx.doi.org/10.1007/s13539-011-0037-3] [PMID: 21966644]
[http://dx.doi.org/10.1073/pnas.0931260100] [PMID: 12702753]
[http://dx.doi.org/10.1079/PNS2004334] [PMID: 15294042]
[http://dx.doi.org/10.1210/er.2002-0012] [PMID: 12588810]
[http://dx.doi.org/10.1016/bs.pmbts.2015.07.016] [PMID: 26477913]
[http://dx.doi.org/10.1113/jphysiol.1988.sp017279] [PMID: 3253447]
[http://dx.doi.org/10.1016/j.mehy.2006.11.043] [PMID: 17376604]
[http://dx.doi.org/10.1096/fj.04-2173com] [PMID: 15629894]
[http://dx.doi.org/10.1172/JCI10268] [PMID: 11018072]
[http://dx.doi.org/10.2174/156652413804486241] [PMID: 22834844]
[http://dx.doi.org/10.1038/cdd.2013.137] [PMID: 24096872]
[http://dx.doi.org/10.1242/jcs.154229] [PMID: 25217629]
[http://dx.doi.org/10.1038/nature00904] [PMID: 12181572]
[http://dx.doi.org/10.1042/bse0420013] [PMID: 17144877]
[http://dx.doi.org/10.1152/ajpendo.00755.2009] [PMID: 20371735]
[http://dx.doi.org/10.1152/ajpcell.00380.2014] [PMID: 25673772]
[http://dx.doi.org/10.1186/s13395-015-0033-y] [PMID: 25834726]
[http://dx.doi.org/10.1113/jphysiol.2014.275545] [PMID: 25128574]
[http://dx.doi.org/10.1113/jphysiol.2014.286740] [PMID: 25565653]
[http://dx.doi.org/10.1073/pnas.0607795103] [PMID: 17053067]
[http://dx.doi.org/10.1073/pnas.0705070104] [PMID: 17609368]
[http://dx.doi.org/10.1152/ajpendo.2001.281.6.E1340] [PMID: 11701451]
[http://dx.doi.org/10.1016/j.ceb.2017.01.005] [PMID: 28232179]
[http://dx.doi.org/10.1038/ncb2329] [PMID: 21892142]
[http://dx.doi.org/10.1152/ajpendo.00410.2012] [PMID: 23531613]
[http://dx.doi.org/10.1096/fj.13-242123] [PMID: 24327607]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-3152] [PMID: 27328730]
[http://dx.doi.org/10.1152/ajpendo.00113.2012] [PMID: 22535746]
[http://dx.doi.org/10.1152/physiol.00041.2007] [PMID: 18556469]
[http://dx.doi.org/10.1158/0008-5472.CAN-13-1052] [PMID: 24197136]
[http://dx.doi.org/10.1007/s13539-014-0141-2] [PMID: 24668658]
[PMID: 22732425]
[http://dx.doi.org/10.1096/fj.13-228486] [PMID: 23825228]
[http://dx.doi.org/10.1007/s00335-016-9659-2] [PMID: 27484057]
[http://dx.doi.org/10.1159/000103376] [PMID: 17643062]
[http://dx.doi.org/10.1152/ajpcell.00066.2016] [PMID: 27281480]
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.05.010] [PMID: 27184957]
[http://dx.doi.org/10.1016/j.febslet.2010.01.056] [PMID: 20132819]
[http://dx.doi.org/10.1016/j.cmet.2009.10.008] [PMID: 19945408]
[http://dx.doi.org/10.1038/nm.3686] [PMID: 25261994]
[http://dx.doi.org/10.1038/s41598-017-02088-2] [PMID: 28515477]
[http://dx.doi.org/10.1016/j.ajpath.2012.12.023] [PMID: 23395093]
[http://dx.doi.org/10.1006/abbi.1993.1479] [PMID: 8215420]
[http://dx.doi.org/10.1152/ajpcell.00192.2009] [PMID: 19955483]
[http://dx.doi.org/10.1002/jcsm.12145] [PMID: 27897407]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3145] [PMID: 21163868]
[http://dx.doi.org/10.1016/j.cellsig.2016.03.005] [PMID: 26976209]
[http://dx.doi.org/10.4161/cc.9.21.13817] [PMID: 21051947]
[http://dx.doi.org/10.1038/srep30340] [PMID: 27459917]
[http://dx.doi.org/10.1007/s13539-011-0028-4] [PMID: 21766055]
[http://dx.doi.org/10.4161/auto.7.5.15102] [PMID: 21412053]
[http://dx.doi.org/10.1002/jcb.23399] [PMID: 22006269]
[http://dx.doi.org/10.1016/j.currproblcancer.2011.01.001] [PMID: 21420558]
[http://dx.doi.org/10.1016/j.appet.2015.04.049] [PMID: 25912786]
[http://dx.doi.org/10.1177/0269216312441382] [PMID: 22450159]
[http://dx.doi.org/10.3109/0284186X.2012.724536] [PMID: 23020528]
[http://dx.doi.org/10.1155/2013/642848] [PMID: 24381940]
[http://dx.doi.org/10.1016/j.lfs.2016.04.029] [PMID: 27117583]
[http://dx.doi.org/10.1016/j.jpainsymman.2010.01.023] [PMID: 20598849]
[http://dx.doi.org/10.1093/jnci/92.4.321] [PMID: 10675381]
[http://dx.doi.org/10.1097/MCO.0b013e328331de63] [PMID: 19741514]
[http://dx.doi.org/10.1113/expphysiol.2013.072496] [PMID: 23625954]
[http://dx.doi.org/10.4236/aar.2016.51002]
[PMID: 18821472]
[PMID: 26000816]
[http://dx.doi.org/10.4236/ojemd.2014.44011]
[http://dx.doi.org/10.1007/s13539-011-0018-6] [PMID: 21475674]
[http://dx.doi.org/10.1074/jbc.M414670200] [PMID: 15653680]
[http://dx.doi.org/10.18632/aging.100075] [PMID: 20157566]
[http://dx.doi.org/10.1016/0006-291X(74)90631-7] [PMID: 4827840]
[http://dx.doi.org/10.1073/pnas.0604392103] [PMID: 16790548]
[http://dx.doi.org/10.1073/pnas.0603968103] [PMID: 16788062]
[http://dx.doi.org/10.1007/s11010-009-0209-z] [PMID: 19618123]
[http://dx.doi.org/10.3390/ijms19040928] [PMID: 29561771]