title: Mitochondria in lung biology and pathology: more than just a powerhouse.
abstract: An explosion of new information about mitochondria reveals that their importance extends well beyond their time-honored function as the "powerhouse of the cell." In this Perspectives article, we summarize new evidence showing that mitochondria are at the center of a reactive oxygen species (ROS)-dependent pathway governing the response to hypoxia and to mitochondrial quality control. The potential role of the mitochondrial genome as a sentinel molecule governing cytotoxic responses of lung cells to ROS stress also is highlighted. Additional attention is devoted to the fate of damaged mitochondrial DNA relative to its involvement as a damage-associated molecular pattern driving adverse lung and systemic cell responses in severe illness or trauma. Finally, emerging strategies for replenishing normal populations of mitochondria after damage, either through promotion of mitochondrial biogenesis or via mitochondrial transfer, are discussed.
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Pediatrics, Chicago, Illinois;
authors.forename: Paul T
authors.initials: PT
authors.lastname: Schumacker
authors.affiliation: University of South Alabama College of Medicine, Department of Pharmacology, Mobile, Alabama; mgillesp@southalabama.edu.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Gillespie
authors.affiliation: Weill Cornell Medical College, Department of Medicine, New York, New York;
authors.forename: Kiichi
authors.initials: K
authors.lastname: Nakahira
authors.affiliation: Weill Cornell Medical College, Department of Medicine, New York, New York;
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.affiliation: The Ohio State University College of Medicine, Department of Internal Medicine, Columbus, Ohio;
authors.forename: Elliott D
authors.initials: ED
authors.lastname: Crouser
authors.affiliation: Duke University School of Medicine, Department of Medicine, Durham, North Carolina, and.
authors.forename: Claude A
authors.initials: CA
authors.lastname: Piantadosi
authors.affiliation: Columbia University Medical Center, Department of Physiology and Cellular Biophysics, New York, New York.
authors.forename: Jahar
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D015415:Biomarkers; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D010100:Oxygen
keywords: hypoxia; lung injury; mitochondrial biogenesis; mitochondrial transfer; mtDNA
references.citation: Chest. 1985 Oct;88(4 Suppl):229S-232S
references.pmid: 4042728
references.citation: Nat Med. 2008 Sep;14(9):949-53
references.pmid: 18690244
references.citation: J Biol Chem. 2009 Dec 25;284(52):36191-36201
references.pmid: 19840931
references.citation: Am J Physiol Lung Cell Mol Physiol. 2011 Dec;301(6):L892-8
references.pmid: 21890512
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7944-9
references.pmid: 10393927
references.citation: Nature. 2010 Mar 4;464(7285):104-7
references.pmid: 20203610
references.citation: Antiviral Res. 2013 Sep;99(3):230-7
references.pmid: 23721943
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11715-20
references.pmid: 9751731
references.citation: Free Radic Biol Med. 2009 Sep 15;47(6):750-9
references.pmid: 19524665
references.citation: Circ Res. 2001 Jun 22;88(12):1259-66
references.pmid: 11420302
references.citation: Cell Metab. 2005 Jun;1(6):393-9
references.pmid: 16054088
references.citation: Physiol Genomics. 2010 Apr 1;41(2):109-19
references.pmid: 20028937
references.citation: PLoS Med. 2013 Dec;10(12):e1001577; discussion e1001577
references.pmid: 24391478
references.citation: Nature. 1970 Mar 21;225(5238):1147-9
references.pmid: 4313870
references.citation: Life Sci. 2007 Sep 15;81(14):1160-6
references.pmid: 17870132
references.citation: J Cell Sci. 2007 Jan 15;120(Pt 2):299-308
references.pmid: 17179207
references.citation: J Biol Chem. 2002 Nov 22;277(47):44932-7
references.pmid: 12244119
references.citation: Sci Rep. 2013;3:1077
references.pmid: 23326634
references.citation: J Biol Chem. 2011 May 6;286(18):16374-85
references.pmid: 21454555
references.citation: Science. 2003 Feb 7;299(5608):896-9
references.pmid: 12574632
references.citation: Circ Res. 2001 Mar 16;88(5):529-35
references.pmid: 11249877
references.citation: Ann Surg. 2013 Oct;258(4):591-6; discussion 596-8
references.pmid: 23979273
references.citation: Respir Res. 2007 Oct 09;8:72
references.pmid: 17925007
references.citation: Nat Immunol. 2011 Mar;12(3):222-30
references.pmid: 21151103
references.citation: Lancet. 2002 Jul 20;360(9328):219-23
references.pmid: 12133657
references.citation: Am J Physiol. 1995 Jun;268(6 Pt 1):L918-25
references.pmid: 7611433
references.citation: Am J Physiol Lung Cell Mol Physiol. 2012 May 1;302(9):L933-40
references.pmid: 22287613
references.citation: Circ Res. 2000 May 12;86(9):960-6
references.pmid: 10807868
references.citation: Cell Death Differ. 2009 Jul;16(7):939-46
references.pmid: 19229244
references.citation: J Immunol. 2013 Feb 15;190(4):1714-24
references.pmid: 23296708
references.citation: J Clin Invest. 1998 Jun 1;101(11):2319-30
references.pmid: 9616203
references.citation: Respir Res. 2009 Sep 23;10:84
references.pmid: 19772669
references.citation: Ann N Y Acad Sci. 2005 May;1042:101-8
references.pmid: 15965051
references.citation: Methods Mol Biol. 2009;554:233-49
references.pmid: 19513678
references.citation: Free Radic Biol Med. 2000 Apr 15;28(8):1161-74
references.pmid: 10889445
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):514-9
references.pmid: 9012815
references.citation: J Immunol. 2008 Feb 15;180(4):2562-72
references.pmid: 18250467
references.citation: Hepatology. 2012 Nov;56(5):1971-82
references.pmid: 22532075
references.citation: Mol Cell Biol. 2011 Sep;31(17):3531-45
references.pmid: 21670147
references.citation: J Neurophysiol. 1972 Jul;35(4):405-28
references.pmid: 4338562
references.citation: EMBO J. 2014 May 2;33(9):994-1010
references.pmid: 24431222
references.citation: Intern Med. 2009;48(9):621-30
references.pmid: 19420806
references.citation: Crit Care. 2010;14(1):R15
references.pmid: 20144219
references.citation: Am J Respir Crit Care Med. 2013 Feb 15;187(4):424-32
references.pmid: 23328522
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L530-5
references.pmid: 15563690
references.citation: Physiol Genomics. 2006 Jun 16;26(1):68-75
references.pmid: 16569776
references.citation: DNA Repair (Amst). 2013 Oct;12(10):856-63
references.pmid: 23890570
references.citation: Antioxid Redox Signal. 2011 Aug 1;15(3):817-29
references.pmid: 20977338
references.citation: Circ Res. 2002 Sep 20;91(6):478-86
references.pmid: 12242265
references.citation: Free Radic Biol Med. 2012 Dec 1;53(11):2043-53
references.pmid: 23000245
references.citation: Am J Respir Crit Care Med. 2003 Feb 15;167(4):570-9
references.pmid: 12480607
references.citation: Autophagy. 2011 Mar;7(3):297-300
references.pmid: 21252623
references.citation: Free Radic Biol Med. 2006 Mar 1;40(5):754-62
references.pmid: 16520228
references.citation: Nature. 2012 May 10;485(7397):251-5
references.pmid: 22535248
references.citation: Am J Respir Crit Care Med. 2011 Aug 1;184(3):328-39
references.pmid: 21562126
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1300-8
references.pmid: 11350811
references.citation: Science. 2001 Apr 20;292(5516):464-8
references.pmid: 11292862
references.citation: Nat Med. 2008 Jan;14(1):64-8
references.pmid: 18084302
references.citation: Nucleic Acids Res. 2009 May;37(8):2539-48
references.pmid: 19264794
references.citation: Cardiovasc Res. 2004 Nov 1;64(2):279-88
references.pmid: 15485687
references.citation: J Biol Chem. 2004 May 21;279(21):22284-93
references.pmid: 14985369
references.citation: Circ Res. 2010 Feb 19;106(3):526-35
references.pmid: 20019331
references.citation: Cell Metab. 2005 Jun;1(6):401-8
references.pmid: 16054089
references.citation: J Immunol. 2012 Jul 1;189(1):433-43
references.pmid: 22675199
references.citation: Am J Physiol. 1982 Aug;243(2):H159-69
references.pmid: 7114227
references.citation: J Biol Chem. 1998 May 8;273(19):11619-24
references.pmid: 9565580
references.citation: FASEB J. 2005 Sep;19(11):1531-3
references.pmid: 15994412
references.citation: Am J Physiol Cell Physiol. 2008 Feb;294(2):C413-22
references.pmid: 18077603
references.citation: Free Radic Biol Med. 2012 Oct 15;53(8):1584-94
references.pmid: 22940620
references.citation: Annu Rev Immunol. 2011;29:707-35
references.pmid: 21219188
references.citation: Mol Cell. 2006 Dec 28;24(6):813-25
references.pmid: 17189185
references.citation: BMC Cancer. 2006 Oct 03;6:235
references.pmid: 17018150
references.citation: Nucleic Acids Res. 2011 Jul;39(12):5098-108
references.pmid: 21398640
references.citation: Physiol Res. 1995;44(6):361-7
references.pmid: 8798271
references.citation: PLoS One. 2013 Aug 12;8(8):e72354
references.pmid: 23951313
references.citation: Physiology (Bethesda). 2013 Nov;28(6):414-22
references.pmid: 24186936
references.citation: Exp Physiol. 2006 Sep;91(5):807-19
references.pmid: 16857720
references.citation: Neonatology. 2013;103(2):91-7
references.pmid: 23154780
references.citation: Biochem J. 2013 Dec 15;456(3):337-46
references.pmid: 24044889
references.citation: Circ Res. 2006 Oct 27;99(9):970-8
references.pmid: 17008601
references.citation: Trends Biochem Sci. 2005 Jun;30(6):294-6
references.pmid: 15950872
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Jul;283(1):L205-10
references.pmid: 12060578
references.citation: Respir Physiol Neurobiol. 2010 Dec 31;174(3):201-11
references.pmid: 20713189
references.citation: Am J Respir Crit Care Med. 2012 Jun 1;185(11):1225-34
references.pmid: 22461369
references.citation: J Biol Chem. 2004 Mar 26;279(13):13044-53
references.pmid: 14722062
references.citation: J Biol Chem. 2008 Feb 8;283(6):3665-3675
references.pmid: 18063578
references.citation: Cancer Res. 2001 Jul 15;61(14):5378-81
references.pmid: 11454679
references.citation: Trends Immunol. 2011 Apr;32(4):157-64
references.pmid: 21334975
references.citation: ACS Chem Biol. 2007 Mar 20;2(3):176-86
references.pmid: 17348629
references.citation: FASEB J. 2001 May;15(7):1267-9
references.pmid: 11344109
references.citation: Nat Med. 2012 Apr 15;18(5):759-65
references.pmid: 22504485
references.citation: Nucleic Acids Res. 1997 Nov 1;25(21):4362-9
references.pmid: 9336469
references.citation: Am J Hum Genet. 1999 May;64(5):1276-81
references.pmid: 10205257
references.citation: Am J Physiol Lung Cell Mol Physiol. 2013 Feb 15;304(4):L287-97
references.pmid: 23241530
references.citation: Free Radic Biol Med. 2011 May 1;50(9):1107-13
references.pmid: 20969951
references.citation: J Transl Med. 2012 Jun 21;10:130
references.pmid: 22720733
references.citation: Mol Cell Biol. 2005 Feb;25(4):1354-66
references.pmid: 15684387
references.citation: Nature. 2011 Jan 13;469(7329):221-5
references.pmid: 21124315
references.citation: Nature. 2002 Jun 27;417(6892):975-8
references.pmid: 12050673
references.citation: Circ Res. 2008 Nov 21;103(11):1232-40
references.pmid: 18845810