title: Effects of early life exposure to ultraviolet C radiation on mitochondrial DNA content, transcription, ATP production, and oxygen consumption in developing Caenorhabditis elegans.
abstract: BACKGROUND
  Mitochondrial DNA (mtDNA) is present in multiple copies per cell and undergoes dramatic amplification during development. The impacts of mtDNA damage incurred early in development are not well understood, especially in the case of types of mtDNA damage that are irreparable, such as ultraviolet C radiation (UVC)-induced photodimers.
  
  
  METHODS
  We exposed first larval stage nematodes to UVC using a protocol that results in accumulated mtDNA damage but permits nuclear DNA (nDNA) repair. We then measured the transcriptional response, as well as oxygen consumption, ATP levels, and mtDNA copy number through adulthood.
  
  
  RESULTS
  Although the mtDNA damage persisted to the fourth larval stage, we observed only a relatively minor ~40% decrease in mtDNA copy number. Transcriptomic analysis suggested an inhibition of aerobic metabolism and developmental processes; mRNA levels for mtDNA-encoded genes were reduced ~50% at 3 hours post-treatment, but recovered and, in some cases, were upregulated at 24 and 48 hours post-exposure. The mtDNA polymerase γ was also induced ~8-fold at 48 hours post-exposure. Moreover, ATP levels and oxygen consumption were reduced in response to UVC exposure, with marked reductions of ~50% at the later larval stages.
  
  
  CONCLUSIONS
  These results support the hypothesis that early life exposure to mitochondrial genotoxicants could result in mitochondrial dysfunction at later stages of life, thereby highlighting the potential health hazards of time-delayed effects of these genotoxicants in the environment.
authors: Nicholas School of the Environment, Duke University, Durham, NC, USA.
authors: Maxwell C K
authors: MC
authors: Leung
authors: John P
authors: JP
authors: Rooney
authors: Ian T
authors: IT
authors: Ryde
authors: Autumn J
authors: AJ
authors: Bernal
authors: Amanda S
authors: AS
authors: Bess
authors: Tracey L
authors: TL
authors: Crocker
authors: Alex Q
authors: AQ
authors: Ji
authors: Joel N
authors: JN
authors: Meyer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D056915:DNA Copy Number Variations; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000528:radiation effects*; D020869:Gene Expression Profiling; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption; D014158:Transcription, Genetic / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate
references: Genome Res. 2009 Jun;19(6):1107-16
references: 19246318
references: Science. 2009 Apr 3;324(5923):92-4
references: 19251593
references: Mitochondrion. 2005 Jun;5(3):173-93
references: 16050983
references: Proc Natl Acad Sci U S A. 1985 Jan;82(2):351-5
references: 2982153
references: Environ Mol Mutagen. 2007 Apr-May;48(3-4):173-8
references: 17358031
references: Nucleic Acids Res. 2009 Apr;37(6):1817-28
references: 19181702
references: Bioinformatics. 2005 Aug 15;21(16):3448-9
references: 15972284
references: WormBook. 2009 Feb 16;:1-24
references: 19248207
references: Arch Biochem Biophys. 2005 Jun 1;438(1):93-102
references: 15910738
references: Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):1088-97
references: 22080153
references: Methods Mol Biol. 2007;372:51-66
references: 18314717
references: Genes Dev. 2003 Aug 1;17(15):1882-93
references: 12869585
references: Mutat Res. 2010 Jan 5;683(1-2):57-67
references: 19879883
references: Methods Mol Biol. 2000;132:365-86
references: 10547847
references: Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):979-91
references: 22728831
references: DNA Repair (Amst). 2012 Aug 1;11(8):684-92
references: 22766155
references: Dev Disabil Res Rev. 2010;16(2):189-99
references: 20818734
references: Mol Biol Cell. 1992 Nov;3(11):1199-213
references: 1457827
references: Biochem Biophys Res Commun. 2002 Feb 15;291(1):8-16
references: 11829454
references: Arch Biochem Biophys. 2001 Nov 15;395(2):158-68
references: 11697852
references: Mitochondrion. 2005 Apr;5(2):89-108
references: 16050976
references: Science. 2006 Mar 10;311(5766):1481-4
references: 16527984
references: Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12133-8
references: 20562347
references: Exp Gerontol. 2002 Aug-Sep;37(8-9):1015-21
references: 12213552
references: J Biochem. 2008 Apr;143(4):449-54
references: 18174190
references: Biochim Biophys Acta. 2003 Jul 14;1638(2):91-105
references: 12853115
references: Mar Genomics. 2010 Mar;3(1):11-8
references: 21798192
references: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D418-24
references: 15608229
references: J Biol Chem. 2001 Aug 24;276(34):32240-6
references: 11410594
references: BMC Physiol. 2008 Apr 02;8:7
references: 18384668
references: Nat Genet. 2008 Feb;40(2):181-8
references: 18223650
references: Mitochondrion. 2010 Aug;10(5):579-81
references: 20197119
references: Aging Cell. 2009 Aug;8(4):380-93
references: 19416129
references: Cell. 2011 Jan 7;144(1):79-91
references: 21215371
references: Exp Gerontol. 2010 Aug;45(7-8):550-7
references: 20172019
references: Biochemistry. 2003 Sep 2;42(34):10269-81
references: 12939156
references: Curr Top Dev Biol. 2007;77:51-83
references: 17222700
references: BMC Mol Biol. 2008 Jan 22;9:9
references: 18211699
references: Biochim Biophys Acta. 2012 Sep-Oct;1819(9-10):970-8
references: 22207204
references: J Mol Biol. 1984 Feb 5;172(4):451-66
references: 6694216
references: Nucleic Acids Res. 2012 Sep;40(16):7916-31
references: 22718972
references: J Biochem Mol Toxicol. 2013 Jan;27(1):28-41
references: 23132756
references: Toxicol Sci. 2008 Nov;106(1):5-28
references: 18566021
references: J Biol Chem. 2012 Mar 16;287(12):9222-9
references: 22194617
references: PLoS One. 2012;7(10):e46503
references: 23056324
references: Front Biosci. 2007 Jan 01;12:1079-93
references: 17127363
references: Mitochondrion. 2010 Mar;10(2):125-36
references: 19900588
references: Biochemistry. 1998 Nov 10;37(45):15933-40
references: 9843399
references: Cell. 2011 Aug 19;146(4):645-58
references: 21854988
references: Genome Biol. 2007;8(5):R70
references: 17472752
references: Biochem J. 2008 Jan 1;409(1):205-13
references: 17714076
references: Nat Methods. 2009 Jan;6(1):47-54
references: 19123269
references: Hum Reprod. 2000 Jul;15 Suppl 2:229-34
references: 11041528
references: Bioinformatics. 2002;18 Suppl 1:S233-40
references: 12169552
references: Methods. 2010 Aug;51(4):444-51
references: 20123023
references: Toxicol Sci. 2009 May;109(1):88-95
references: 19299418
references: Acta Biochim Pol. 2006;53(3):485-95
references: 16951738
references: Aging Cell. 2007 Apr;6(2):179-88
references: 17286610
references: J Exp Zool A Comp Exp Biol. 2006 Sep 1;305(9):720-30
references: 16902959
references: DNA Repair (Amst). 2012 Nov 1;11(11):857-63
references: 22959841