title: Mitochondrial oxidative phosphorylation TRAP(1)ped in tumor cells.
abstract: Many tumors undergo a dramatic metabolic shift known as the Warburg effect in which glucose utilization is favored and oxidative phosphorylation is downregulated, even when oxygen availability is plentiful. However, the mechanistic basis for this switch has remained unclear. Recently several independent groups identified tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial molecular chaperone of the heat shock protein 90 (Hsp90) family, as a key modulator of mitochondrial respiration. Although all reports agree that this activity of TRAP1 has important implications for neoplastic progression, data from the different groups only partially overlap, suggesting that TRAP1 may have complex and possibly contextual effects on tumorigenesis. In this review we analyze these recent findings and attempt to reconcile these observations.
authors.affiliation: CNR Institute of Neuroscience, University of Padova, 35121 Padova, Italy; Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy. Electronic address: rasola@bio.unipd.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rasola
authors.affiliation: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Len
authors.initials: L
authors.lastname: Neckers
authors.affiliation: Department of Cell Biology, University of Geneva, CH-1211 Geneva 4, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Picard
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation
chemical_list: D018841:HSP90 Heat-Shock Proteins
keywords: ROS; TRAP1; cancer metabolism; chaperones; mitochondria
references.citation: Cancer Discov. 2013 Jul;3(7):730-41
references.pmid: 23796461
references.citation: Oncologist. 2011;16 Suppl 2:4-13
references.pmid: 21346035
references.citation: Oncogene. 2006 Aug 7;25(34):4777-86
references.pmid: 16892090
references.citation: J Cereb Blood Flow Metab. 2009 Feb;29(2):365-74
references.pmid: 18985056
references.citation: Kidney Int. 2014 Jun;85(6):1310-7
references.pmid: 24152966
references.citation: Cell. 2012 Mar 30;149(1):22-35
references.pmid: 22464321
references.citation: Oncogene. 2009 Oct 22;28(42):3681-8
references.pmid: 19648961
references.citation: Oncogene. 2010 Feb 4;29(5):625-34
references.pmid: 19946328
references.citation: J Clin Invest. 2013 Jul;123(7):2907-20
references.pmid: 23921130
references.citation: J Gen Physiol. 1927 Mar 7;8(6):519-30
references.pmid: 19872213
references.citation: Biochim Biophys Acta. 2012 Mar;1823(3):605-6
references.pmid: 22341738
references.citation: Cell Death Dis. 2013 Jan 17;4:e467
references.pmid: 23328674
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3260-5
references.pmid: 10737792
references.citation: J Neurochem. 2009 Jul;110(2):496-508
references.pmid: 19490362
references.citation: FEBS J. 2010 Apr;277(8):1929-38
references.pmid: 20236315
references.citation: Biochim Biophys Acta. 2012 Aug;1826(1):238-54
references.pmid: 22554970
references.citation: Curr Opin Genet Dev. 2011 Feb;21(1):67-72
references.pmid: 21074987
references.citation: J Biol Chem. 2007 Jul 13;282(28):20553-60
references.pmid: 17513296
references.citation: Cell. 2008 Sep 5;134(5):703-7
references.pmid: 18775299
references.citation: J Biol Chem. 2000 Feb 4;275(5):3305-12
references.pmid: 10652318
references.citation: Cancer Cell. 2005 Jan;7(1):77-85
references.pmid: 15652751
references.citation: Cell. 2007 Oct 19;131(2):257-70
references.pmid: 17956728
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: PLoS Biol. 2007 Jul;5(7):e172
references.pmid: 17579517
references.citation: Nature. 2012 Nov 15;491(7424):364-73
references.pmid: 23151579
references.citation: Semin Cancer Biol. 2009 Feb;19(1):4-11
references.pmid: 19101633
references.citation: Am J Pathol. 2010 Jan;176(1):393-401
references.pmid: 19948822
references.citation: Oncogene. 2005 Feb 17;24(8):1455-60
references.pmid: 15608681
references.citation: EMBO J. 2012 Jun 26;31(14):3038-62
references.pmid: 22735187
references.citation: Trends Biochem Sci. 2013 May;38(5):253-62
references.pmid: 23507089
references.citation: Hum Mol Genet. 2013 Jul 15;22(14):2829-41
references.pmid: 23525905
references.citation: Biochem J. 2009 Apr 15;419(2):369-75
references.pmid: 19143589
references.citation: Biochim Biophys Acta. 2012 Feb;1823(2):348-57
references.pmid: 22178133
references.citation: PLoS One. 2012;7(12):e51912
references.pmid: 23284813
references.citation: Curr Opin Neurobiol. 2013 Feb;23(1):100-8
references.pmid: 23206589
references.citation: Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):1225-30
references.pmid: 20381449
references.citation: Cancer Cell. 2012 Mar 20;21(3):297-308
references.pmid: 22439925
references.citation: J Biol Chem. 2006 Nov 3;281(44):33313-24
references.pmid: 16968702
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):726-31
references.pmid: 20080742
references.citation: Cell Calcium. 2011 Sep;50(3):222-33
references.pmid: 21601280
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1604-12
references.pmid: 23564345
references.citation: Nat Commun. 2013;4:2139
references.pmid: 23842546
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Mol Cancer. 2012 Sep 14;11:69
references.pmid: 22978347
references.citation: Cell Death Dis. 2013 Oct 17;4:e858
references.pmid: 24136222
references.citation: J Clin Invest. 2013 Sep;123(9):3652-8
references.pmid: 23999438
references.citation: Nat Rev Cancer. 2013 Sep;13(9):611-23
references.pmid: 23969692
references.citation: Proc Natl Acad Sci U S A. 2010 May 11;107(19):8788-93
references.pmid: 20421486
references.citation: J Biol Chem. 1995 Feb 24;270(8):3574-81
references.pmid: 7876093
references.citation: Biochim Biophys Acta. 2012 Dec;1826(2):423-33
references.pmid: 22841746
references.citation: J Clin Invest. 2013 Sep;123(9):3678-84
references.pmid: 23999442
references.citation: PLoS One. 2008 Mar 19;3(3):e1852
references.pmid: 18350175
references.citation: Exp Cell Res. 2000 Oct 10;260(1):30-9
references.pmid: 11010808
references.citation: Science. 2010 Dec 3;330(6009):1340-4
references.pmid: 21127244
references.citation: Curr Opin Genet Dev. 2010 Feb;20(1):51-6
references.pmid: 19942427
references.citation: Hum Mol Genet. 2008 Apr 1;17(7):986-95
references.pmid: 18156159
references.citation: Mol Cell. 2014 Jan 23;53(2):330-43
references.pmid: 24462206
references.citation: Biochim Biophys Acta. 2011 Jun;1807(6):568-76
references.pmid: 20804724
references.citation: Cancer Lett. 2009 Jun 28;279(1):39-46
references.pmid: 19217207
references.citation: Nat Rev Cancer. 2011 Feb;11(2):85-95
references.pmid: 21258394
references.citation: Cancer Cell. 2005 Aug;8(2):143-53
references.pmid: 16098467
references.citation: J Biol Chem. 2004 Oct 8;279(41):42503-15
references.pmid: 15292218
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-24
references.pmid: 15647368
references.citation: Oncogene. 2006 Aug 7;25(34):4683-96
references.pmid: 16892082
references.citation: PLoS Genet. 2012 Feb;8(2):e1002488
references.pmid: 22319455
references.citation: Mitochondrion. 2013 May;13(3):246-53
references.pmid: 22960576
references.citation: Nat Rev Cancer. 2009 Oct;9(10):691-700
references.pmid: 19759539
references.citation: Biochem J. 1929;23(3):536-45
references.pmid: 16744238
references.citation: Cell Metab. 2013 Jun 4;17(6):988-999
references.pmid: 23747254
references.citation: Nat Rev Cancer. 2011 May;11(5):325-37
references.pmid: 21508971
references.citation: J Biol Chem. 2008 Apr 25;283(17):11677-88
references.pmid: 18287101
references.citation: Genes Dev. 2012 May 1;26(9):877-90
references.pmid: 22549953
references.citation: Int J Biochem Cell Biol. 2014 May;50:10-23
references.pmid: 24513530
references.citation: Stress. 2007 Nov;10(4):342-50
references.pmid: 17853063
references.citation: Cancer Cell. 2012 Sep 11;22(3):331-44
references.pmid: 22975376
references.citation: Cancer Cell. 2012 Oct 16;22(4):547-60
references.pmid: 23079663
references.citation: Biochim Biophys Acta. 2012 Dec;1826(2):370-84
references.pmid: 22750268
references.citation: Cell Death Dis. 2013 Oct 10;4:e851
references.pmid: 24113185
references.citation: Oncogene. 2012 Sep 6;31(36):3999-4011
references.pmid: 22231450
references.citation: Nat Rev Cancer. 2008 Sep;8(9):705-13
references.pmid: 19143055
references.citation: Cell. 2003 Jan 10;112(1):41-50
references.pmid: 12526792
references.citation: Clin Cancer Res. 2012 Oct 15;18(20):5546-53
references.pmid: 23071356
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Int J Biochem Cell Biol. 2014 Mar;48:11-7
references.pmid: 24397955
references.citation: World J Gastroenterol. 2012 Nov 7;18(41):5965-71
references.pmid: 23139614