title: Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress.
abstract: Nucleus-encoded regulatory factors are major contributors to mitochondrial biogenesis and function. Several act within the organelle to regulate mitochondrial transcription and translation while others direct the expression of nuclear genes encoding the respiratory chain and other oxidative functions. Loss-of-function studies for many of these factors reveal a wide spectrum of phenotypes. These range from embryonic lethality and severe respiratory chain deficiency to relatively mild mitochondrial defects seen only under conditions of physiological stress. The PGC-1 family of regulated coactivators (PGC-1α, PGC-1β and PRC) plays an important integrative role through their interactions with transcription factors (NRF-1, NRF-2, ERRα, CREB, YY1 and others) that control respiratory gene expression. In addition, recent evidence suggests that PGC-1 coactivators may balance the cellular response to oxidant stress by promoting a pro-oxidant environment or by orchestrating an inflammatory response to severe metabolic stress. These pathways may serve as essential links between the energy generating functions of mitochondria and the cellular REDOX environment associated with longevity, senescence and disease. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.
authors.affiliation: Department of Cell and Molecular Biology, Northwestern Medical School, Chicago, IL 60611, USA. rsc248@northwestern.edu
authors.forename: Richard C
authors.initials: RC
authors.lastname: Scarpulla
mesh_terms: D000818:Animals; D004579:Electron Transport / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1
references.citation: Mol Cancer Res. 2010 Jan;8(1):1-14
references.pmid: 20068066
references.citation: J Biol Chem. 2000 Jan 28;275(4):2295-304
references.pmid: 10644678
references.citation: FASEB J. 2002 Dec;16(14):1879-86
references.pmid: 12468452
references.citation: Cell Metab. 2005 Apr;1(4):259-71
references.pmid: 16054070
references.citation: Mol Cell Biol. 1988 Aug;8(8):3496-509
references.pmid: 3211148
references.citation: Annu Rev Biochem. 1985;54:1015-69
references.pmid: 2862839
references.citation: Annu Rev Biochem. 1996;65:563-607
references.pmid: 8811190
references.citation: J Clin Invest. 2000 Oct;106(7):847-56
references.pmid: 11018072
references.citation: Gene. 2005 Oct 24;360(1):65-77
references.pmid: 16126350
references.citation: PLoS One. 2010 Jul 22;5(7):e11707
references.pmid: 20661474
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5223-8
references.pmid: 17360356
references.citation: Trends Biochem Sci. 2010 Dec;35(12):669-75
references.pmid: 20863707
references.citation: Biochem J. 2003 Jul 1;373(Pt 1):155-65
references.pmid: 12678921
references.citation: Mitochondrion. 2011 Jul;11(4):544-52
references.pmid: 21497207
references.citation: Genes Dev. 2003 Jan 15;17(2):240-55
references.pmid: 12533512
references.citation: BMC Genomics. 2008 Jan 14;9:18
references.pmid: 18194548
references.citation: J Biol Chem. 1989 Aug 25;264(24):14361-8
references.pmid: 2547796
references.citation: Nature. 2010 Apr 29;464(7293):1313-9
references.pmid: 20357764
references.citation: Mitochondrion. 2004 Apr;3(5):251-9
references.pmid: 16120358
references.citation: Genes Dev. 1993 Dec;7(12A):2431-45
references.pmid: 8253388
references.citation: Genes Dev. 1993 Mar;7(3):380-92
references.pmid: 8383622
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7111-6
references.pmid: 12764228
references.citation: AIDS Res Hum Retroviruses. 1999 Jun 10;15(9):821-7
references.pmid: 10381170
references.citation: Biochim Biophys Acta. 2002 Jun 7;1576(1-2):1-14
references.pmid: 12031478
references.citation: Hum Mol Genet. 2005 Jul 1;14(13):1775-83
references.pmid: 15888483
references.citation: Science. 2002 Apr 12;296(5566):349-52
references.pmid: 11951046
references.citation: Mol Cell Biol. 1995 Jan;15(1):102-11
references.pmid: 7799916
references.citation: Physiol Rev. 2009 Jul;89(3):1025-78
references.pmid: 19584320
references.citation: Genes Dev. 1993 Apr;7(4):671-82
references.pmid: 8458579
references.citation: Gene. 2007 Apr 15;391(1-2):198-208
references.pmid: 17300881
references.citation: J Biol Chem. 1997 Apr 11;272(15):10175-81
references.pmid: 9092564
references.citation: Cell Metab. 2007 Jul;6(1):25-37
references.pmid: 17618854
references.citation: Mol Cell Proteomics. 2003 Nov;2(11):1205-16
references.pmid: 14514796
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6472-7
references.pmid: 15087503
references.citation: Cell Metab. 2009 Apr;9(4):386-97
references.pmid: 19356719
references.citation: Cell Metab. 2011 May 4;13(5):527-39
references.pmid: 21531335
references.citation: Annu Rev Genet. 1990;24:91-113
references.pmid: 2088182
references.citation: Cell. 1999 Jul 9;98(1):115-24
references.pmid: 10412986
references.citation: J Biol Chem. 1993 Jan 15;268(2):1109-17
references.pmid: 8093450
references.citation: Mol Cell Biol. 1997 Sep;17(9):5400-9
references.pmid: 9271417
references.citation: Nature. 2009 Apr 23;458(7241):1056-60
references.pmid: 19262508
references.citation: FEBS Lett. 2008 Jan 9;582(1):46-53
references.pmid: 18036349
references.citation: PLoS One. 2009 Nov 23;4(11):e7964
references.pmid: 19956726
references.citation: Annu Rev Genet. 2005;39:359-407
references.pmid: 16285865
references.citation: J Biol Chem. 2009 Jan 23;284(4):2307-19
references.pmid: 19036724
references.citation: Circ Res. 2004 Sep 17;95(6):568-78
references.pmid: 15375023
references.citation: Mol Cell Biol. 2005 Jul;25(14):6225-34
references.pmid: 15988031
references.citation: Mol Cell. 2004 Nov 5;16(3):399-411
references.pmid: 15525513
references.citation: Mol Cell Biol. 1995 Jun;15(6):3012-22
references.pmid: 7539101
references.citation: Cancer Cell. 2010 Jan 19;17(1):41-52
references.pmid: 20129246
references.citation: Exp Cell Res. 1997 Feb 25;231(1):141-8
references.pmid: 9056421
references.citation: Am J Clin Nutr. 2011 Apr;93(4):884S-90
references.pmid: 21289221
references.citation: Biochim Biophys Acta. 2010 Aug;1804(8):1676-83
references.pmid: 20005308
references.citation: Mol Cell Biol. 2001 Jun;21(11):3738-49
references.pmid: 11340167
references.citation: J Physiol Biochem. 2011 Sep;67(3):359-70
references.pmid: 21394548
references.citation: Biochim Biophys Acta. 1998 Jun 5;1381(1):113-22
references.pmid: 9659378
references.citation: Cancer Cell. 2011 Mar 8;19(3):416-28
references.pmid: 21397863
references.citation: Cell. 1998 Mar 20;92(6):829-39
references.pmid: 9529258
references.citation: Mol Cell Biol. 1991 Nov;11(11):5631-8
references.pmid: 1656236
references.citation: J Biol Chem. 2008 Feb 8;283(6):3120-3129
references.pmid: 18077450
references.citation: Mol Endocrinol. 2009 Jan;23(1):2-10
references.pmid: 19008463
references.citation: Biochim Biophys Acta. 2002 Apr 12;1574(3):359-64
references.pmid: 11997103
references.citation: Mitochondrion. 2010 Aug;10(5):516-27
references.pmid: 20561910
references.citation: Biochim Biophys Acta. 1999 Feb 9;1410(2):103-23
references.pmid: 10076021
references.citation: Am J Physiol. 1990 Mar;258(3 Pt 1):C377-89
references.pmid: 2138418
references.citation: J Biol Chem. 1995 Nov 3;270(44):26433-40
references.pmid: 7592858
references.citation: Nature. 2001 Sep 13;413(6852):179-83
references.pmid: 11557984
references.citation: Mitochondrion. 2007 May;7(3):195-203
references.pmid: 17161026
references.citation: J Biol Chem. 1988 Jun 5;263(16):7767-75
references.pmid: 2897364
references.citation: Physiol Rev. 2004 Jan;84(1):277-359
references.pmid: 14715917
references.citation: PLoS Biol. 2006 Nov;4(11):e369
references.pmid: 17090215
references.citation: Mol Cell. 2011 Jun 10;42(5):561-8
references.pmid: 21658599
references.citation: Cell Metab. 2007 May;5(5):345-56
references.pmid: 17488637
references.citation: Mol Cell Biol. 2003 Nov;23(22):7947-56
references.pmid: 14585956
references.citation: Cell. 2010 Nov 24;143(5):802-12
references.pmid: 21094524
references.citation: Eur J Biochem. 1998 Jan 15;251(1-2):164-74
references.pmid: 9492280
references.citation: Cell Cycle. 2008 Apr 15;7(8):1054-66
references.pmid: 18414044
references.citation: Genes Dev. 2008 Jul 15;22(14):1948-61
references.pmid: 18628400
references.citation: J Biol Chem. 2007 Oct 12;282(41):30014-21
references.pmid: 17702743
references.citation: Biochim Biophys Acta. 2011 Aug;1812(8):1032-40
references.pmid: 21172432
references.citation: PLoS Biol. 2005 Apr;3(4):e101
references.pmid: 15760270
references.citation: Mol Biol Cell. 2007 Sep;18(9):3225-36
references.pmid: 17581862
references.citation: Genes Dev. 1989 Sep;3(9):1372-83
references.pmid: 2558055
references.citation: J Biol Chem. 1997 Dec 12;272(50):31693-9
references.pmid: 9395511
references.citation: Nat Genet. 1997 Jul;16(3):226-34
references.pmid: 9207786
references.citation: J Biol Chem. 2011 May 13;286(19):16958-66
references.pmid: 21454513
references.citation: Cell Metab. 2010 Dec 1;12(6):662-7
references.pmid: 21109198
references.citation: Cell. 2004 Oct 1;119(1):121-35
references.pmid: 15454086
references.citation: J Biol Chem. 2002 Apr 19;277(16):13918-25
references.pmid: 11854298
references.citation: Biochim Biophys Acta. 1999 Aug 4;1412(3):295-300
references.pmid: 10482792
references.citation: Endocr Rev. 2008 Oct;29(6):677-96
references.pmid: 18664618
references.citation: Physiol Rev. 2008 Apr;88(2):611-38
references.pmid: 18391175
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1418-23
references.pmid: 17229846
references.citation: Ann Med. 2010 Apr;42(3):161-70
references.pmid: 20384432
references.citation: Nat Genet. 1999 Jan;21(1):133-7
references.pmid: 9916807
references.citation: Genome Res. 2004 Aug;14(8):1562-74
references.pmid: 15256515
references.citation: J Biol Chem. 2008 May 2;283(18):11935-46
references.pmid: 18222924
references.citation: Cell. 2007 Jul 27;130(2):273-85
references.pmid: 17662942
references.citation: EMBO J. 2007 Apr 4;26(7):1913-23
references.pmid: 17347648
references.citation: Mol Cell Biol. 2004 Jul;24(13):5844-9
references.pmid: 15199140
references.citation: Cell Metab. 2007 Jan;5(1):35-46
references.pmid: 17189205
references.citation: Annu Rev Biochem. 1991;60:281-319
references.pmid: 1883198
references.citation: FEBS J. 2010 Feb;277(3):713-25
references.pmid: 20067526
references.citation: Biochem Biophys Res Commun. 2003 Oct 24;310(3):779-84
references.pmid: 14550271
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17031-6
references.pmid: 19805069
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15066-71
references.pmid: 12417746
references.citation: Prog Nucleic Acid Res Mol Biol. 1998;58:41-78
references.pmid: 9308363
references.citation: J Cell Biol. 2007 Jun 18;177(6):1029-36
references.pmid: 17562787
references.citation: J Biol Chem. 1997 Feb 28;272(9):5899-908
references.pmid: 9038208
references.citation: J Biol Chem. 2008 May 2;283(18):12102-11
references.pmid: 18343819
references.citation: Nature. 2007 Nov 29;450(7170):736-40
references.pmid: 18046414
references.citation: J Biol Chem. 2006 Sep 1;281(35):25791-802
references.pmid: 16825194
references.citation: Cell Metab. 2007 Jul;6(1):13-24
references.pmid: 17618853
references.citation: Cancer Metastasis Rev. 2010 Jun;29(2):273-83
references.pmid: 20390322
references.citation: J Biol Chem. 2011 Nov 18;286(46):39715-25
references.pmid: 21937425
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-52
references.pmid: 18794531
references.citation: Gene. 2006 Jun 7;374:39-49
references.pmid: 16516409
references.citation: Cell. 2005 Feb 25;120(4):483-95
references.pmid: 15734681
references.citation: Nat Cell Biol. 2007 Mar;9(3):339-46
references.pmid: 17277770
references.citation: Mol Cell Biol. 1999 Oct;19(10):7237-44
references.pmid: 10490658
references.citation: J Biol Chem. 1999 Nov 19;274(47):33426-32
references.pmid: 10559224
references.citation: Gene. 1998 Jun 15;213(1-2):133-40
references.pmid: 9714607
references.citation: Cancer Cell. 2007 May;11(5):407-20
references.pmid: 17482131
references.citation: Biochemistry. 2010 Jan 19;49(2):304-11
references.pmid: 20000467
references.citation: Nat Genet. 1998 Mar;18(3):231-6
references.pmid: 9500544
references.citation: J Biol Chem. 2000 Apr 28;275(17):13134-41
references.pmid: 10777619
references.citation: Mol Cell Biol. 2006 Oct;26(20):7409-19
references.pmid: 16908542
references.citation: J Biol Chem. 2003 Aug 15;278(33):30843-8
references.pmid: 12807885
references.citation: Genes Dev. 1990 Jun;4(6):1023-34
references.pmid: 2166701
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12017-22
references.pmid: 17609368
references.citation: Mol Endocrinol. 2008 Mar;22(3):609-22
references.pmid: 18048642
references.citation: Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1340-6
references.pmid: 11701451
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1309-13
references.pmid: 8108407
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878
references.citation: Mol Cell Biochem. 2000 Jul;210(1-2):47-52
references.pmid: 10976757
references.citation: Mol Cell Biol. 2005 Feb;25(4):1354-66
references.pmid: 15684387
references.citation: J Biol Chem. 1994 Jan 7;269(1):105-13
references.pmid: 8276781
references.citation: Biochem Cell Biol. 2008 Feb;86(1):46-56
references.pmid: 18364745
references.citation: FASEB J. 2003 Apr;17(6):675-81
references.pmid: 12665481
references.citation: J Cell Sci. 2010 Aug 1;123(Pt 15):2565-75
references.pmid: 20587593
references.citation: J Biol Chem. 2002 Jan 18;277(3):1645-8
references.pmid: 11733490
references.citation: Cell Biochem Biophys. 1999;30(2):243-65
references.pmid: 10356644
references.citation: J Biol Chem. 1997 Jul 25;272(30):18732-9
references.pmid: 9228045
references.citation: Mol Cell. 2010 Dec 22;40(6):893-904
references.pmid: 21172655
references.citation: PLoS One. 2009 Sep 09;4(9):e6935
references.pmid: 19742324
references.citation: Mol Cell Biol. 2001 Jan;21(2):644-54
references.pmid: 11134350
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6570-5
references.pmid: 15100410
references.citation: Gene. 2008 Dec 31;427(1-2):58-64
references.pmid: 18852034
references.citation: Genes Dev. 2004 Feb 15;18(4):357-68
references.pmid: 15004004