title: About the dangers, costs and benefits of living an aerobic lifestyle.
abstract: The era in which ROS (reactive oxygen species) were simply the 'bad boys of biology' is clearly over. High levels of ROS are still rightfully considered to be toxic to many cellular processes and, as such, contribute to disease conditions and cell death. However, the high toxicity of ROS is also extremely beneficial, particularly as it is used to kill invading micro-organisms during mammalian host defence. Moreover, a transient, often more localized, increase in ROS levels appears to play a major role in signal transduction processes and positively affects cell growth, development and differentiation. At the heart of all these processes are redox-regulated proteins, which use oxidation-sensitive cysteine residues to control their function and by extension the function of the pathways that they are part of. Our work has contributed to changing the view about ROS through: (i) our characterization of Hsp33 (heat-shock protein 33), one of the first redox-regulated proteins identified, whose function is specifically activated by ROS, (ii) the development of quantitative tools that reveal extensive redox-sensitive processes in bacteria and eukaryotes, and (iii) the discovery of a link between early exposure to oxidants and aging. Our future research programme aims to generate an integrated and system-wide view of the beneficial and deleterious effects of ROS with the central goal to develop more effective antioxidant strategies and more powerful antimicrobial agents.
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Daniela
authors.initials: D
authors.lastname: Knoefler
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Lars I O
authors.initials: LI
authors.lastname: Leichert
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Maike
authors.initials: M
authors.lastname: Thamsen
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Cremers
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Dana
authors.initials: D
authors.lastname: Reichmann
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gray
authors.affiliation: *Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, U.S.A.
authors.forename: Wei-Yun
authors.initials: WY
authors.lastname: Wholey
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
mesh_terms: D000332:Aerobiosis / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species
references.citation: Antioxid Redox Signal. 2009 May;11(5):997-1014
references.pmid: 18999917
references.citation: J Gerontol. 1956 Jul;11(3):298-300
references.pmid: 13332224
references.citation: Cell Signal. 2012 May;24(5):981-90
references.pmid: 22286106
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: Free Radic Biol Med. 2010 Mar 1;48(5):642-55
references.pmid: 20036736
references.citation: Aging Cell. 2009 Feb;8(1):73-5
references.pmid: 19077044
references.citation: Nat Genet. 2005 Aug;37(8):894-8
references.pmid: 16041374
references.citation: Free Radic Biol Med. 2010 Dec 1;49(11):1603-16
references.pmid: 20840865
references.citation: Annu Rev Biochem. 1999;68:89-125
references.pmid: 10872445
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5785-90
references.pmid: 22451939
references.citation: J Biol Chem. 2008 Jun 20;283(25):16961-5
references.pmid: 18420576
references.citation: Biochim Biophys Acta. 2014 Aug;1844(8):1335-43
references.pmid: 24657586
references.citation: Mass Spectrom Rev. 2014 Jan-Feb;33(1):21-48
references.pmid: 24114980
references.citation: Nat Struct Mol Biol. 2007 Jun;14(6):556-63
references.pmid: 17515905
references.citation: Cell. 2012 Mar 2;148(5):947-57
references.pmid: 22385960
references.citation: Annu Rev Microbiol. 2013;67:141-60
references.pmid: 23768204
references.citation: Science. 2005 Nov 4;310(5749):847-50
references.pmid: 16272120
references.citation: Mol Cell. 2005 Feb 4;17(3):381-92
references.pmid: 15694339
references.citation: Biochim Biophys Acta. 2009 Oct;1790(10):1005-14
references.pmid: 19524016
references.citation: EMBO J. 2004 Jan 14;23(1):160-8
references.pmid: 14685279
references.citation: Toxicology. 2002 Dec 27;181-182:223-7
references.pmid: 12505315
references.citation: Mol Cell. 2012 Sep 14;47(5):767-76
references.pmid: 22819323
references.citation: Annu Rev Biochem. 2009;78:605-47
references.pmid: 19344251
references.citation: Cell. 2008 Nov 14;135(4):691-701
references.pmid: 19013278
references.citation: Antioxid Redox Signal. 2013 Feb 20;18(6):642-60
references.pmid: 22881869
references.citation: Arch Biochem Biophys. 2012 Sep 15;525(2):161-9
references.pmid: 22381957
references.citation: Mech Ageing Dev. 2005 Mar;126(3):439-43
references.pmid: 15664632
references.citation: Free Radic Biol Med. 2014 Jan;66:75-87
references.pmid: 23899494
references.citation: Science. 2002 Dec 20;298(5602):2398-401
references.pmid: 12471266
references.citation: Nat Chem Biol. 2008 May;4(5):278-86
references.pmid: 18421291
references.citation: J Gerontol A Biol Sci Med Sci. 2009 Dec;64(12):1212-20
references.pmid: 19776219
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):813-24
references.pmid: 17848967
references.citation: Antioxid Redox Signal. 2011 Mar 15;14(6):1023-37
references.pmid: 20649472
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8197-202
references.pmid: 18287020
references.citation: Nat Methods. 2006 Apr;3(4):281-6
references.pmid: 16554833
references.citation: Mol Cell. 2014 Mar 6;53(5):689-99
references.pmid: 24560923
references.citation: Ann N Y Acad Sci. 2001 Apr;928:22-38
references.pmid: 11795513