title: Electron Transport Chain Remodeling by GSK3 during Oogenesis Connects Nutrient State to Reproduction.
abstract: Reproduction is heavily influenced by nutrition and metabolic state. Many common reproductive disorders in humans are associated with diabetes and metabolic syndrome. We characterized the metabolic mechanisms that support oogenesis and found that mitochondria in mature Drosophila oocytes enter a low-activity state of respiratory quiescence by remodeling the electron transport chain (ETC). This shift in mitochondrial function leads to extensive glycogen accumulation late in oogenesis and is required for the developmental competence of the oocyte. Decreased insulin signaling initiates ETC remodeling and mitochondrial respiratory quiescence through glycogen synthase kinase 3 (GSK3). Intriguingly, we observed similar ETC remodeling and glycogen uptake in maturing Xenopus oocytes, suggesting that these processes are evolutionarily conserved aspects of oocyte development. Our studies reveal an important link between metabolism and oocyte maturation.
authors.affiliation: Department of Embryology, Carnegie Institution of Washington, 3520 San Martin Drive, Baltimore, MD 21218, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Sieber
authors.affiliation: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Thomsen
authors.affiliation: Department of Embryology, Carnegie Institution of Washington, 3520 San Martin Drive, Baltimore, MD 21218, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: spradling@ciwemb.edu.
authors.forename: Allan C
authors.initials: AC
authors.lastname: Spradling
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009866:Oogenesis; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D045222:Electron Transport Chain Complex Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D006003:Glycogen; D051058:Oncogene Protein v-akt; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3
references.citation: Nat Rev Mol Cell Biol. 2001 Oct;2(10):769-76
references.pmid: 11584304
references.citation: Reprod Biomed Online. 2014 Jan;28(1):99-105
references.pmid: 24268727
references.citation: Mitochondrion. 2011 Sep;11(5):797-813
references.pmid: 20933103
references.citation: Cell Metab. 2009 Dec;10(6):481-90
references.pmid: 19945405
references.citation: Dev Biol. 1977 Jun;57(2):393-402
references.pmid: 406151
references.citation: PLoS Genet. 2015 Feb 19;11(2):e1004989
references.pmid: 25695427
references.citation: Mol Cell. 2004 May 21;14(4):416-8
references.pmid: 15149589
references.citation: Annu Rev Physiol. 1990;52:523-42
references.pmid: 2158767
references.citation: PLoS One. 2013 Jun 04;8(6):e65125
references.pmid: 23750237
references.citation: Methods. 2014 Jun 15;68(1):105-15
references.pmid: 24631891
references.citation: Nature. 2001 Dec 13;414(6865):799-806
references.pmid: 11742412
references.citation: Annu Rev Plant Biol. 2011;62:79-104
references.pmid: 21332361
references.citation: Biol Reprod. 2000 Jun;62(6):1866-74
references.pmid: 10819794
references.citation: Genes Dev. 1998 Aug 15;12(16):2488-98
references.pmid: 9716402
references.citation: G3 (Bethesda). 2014 Mar 12;4(5):839-50
references.pmid: 24622332
references.citation: Reproduction. 2014 Jul;148(1):R15-27
references.pmid: 24760880
references.citation: Dev Biol. 2006 Nov 1;299(1):1-11
references.pmid: 16970938
references.citation: Science. 2005 Aug 12;309(5737):1071-3
references.pmid: 16099985
references.citation: PLoS One. 2014 Feb 05;9(2):e87327
references.pmid: 24505284
references.citation: Trends Biochem Sci. 2002 Jul;27(7):352-60
references.pmid: 12114024
references.citation: Mol Cell. 2006 Mar 17;21(6):749-60
references.pmid: 16543145
references.citation: Dev Biol. 2004 Feb 15;266(2):310-21
references.pmid: 14738879
references.citation: Womens Health (Lond). 2015 Mar;11(2):137-49
references.pmid: 25776288
references.citation: Genetics. 2002 Apr;160(4):1511-8
references.pmid: 11973306
references.citation: Cell Metab. 2012 Jan 4;15(1):122-7
references.pmid: 22197324
references.citation: Hum Reprod. 1986 Apr;1(3):183-4
references.pmid: 3624426
references.citation: Eur J Cell Biol. 1994 Feb;63(1):52-60
references.pmid: 8005105
references.citation: Annu Rev Physiol. 1985;47:645-63
references.pmid: 3888081
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6965-70
references.pmid: 9618522
references.citation: Biochem J. 1992 May 15;284 ( Pt 1):1-13
references.pmid: 1599389
references.citation: Curr Biol. 2015 Apr 20;25(8):993-1004
references.pmid: 25802149
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):187-92
references.pmid: 17189423
references.citation: Cell. 1993 Mar 12;72(5):649-51
references.pmid: 8453660
references.citation: Mol Cell. 2004 May 7;14(3):395-403
references.pmid: 15125842
references.citation: Reproduction. 2010 Apr;139(4):685-95
references.pmid: 20089664
references.citation: Dev Biol. 2001 Mar 1;231(1):265-78
references.pmid: 11180967
references.citation: Trends Endocrinol Metab. 2005 May-Jun;16(4):183-9
references.pmid: 15860415
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7996-8001
references.pmid: 12808136
references.citation: J Biol. 2003;2(3):18
references.pmid: 12974982
references.citation: Nature. 1997 Oct 30;389(6654):994-9
references.pmid: 9353126
references.citation: Nat Methods. 2008 Jan;5(1):49-51
references.pmid: 18084299
references.citation: J Biol. 2003;2(3):20
references.pmid: 12908874
references.citation: Curr Med Chem. 2014;21(35):3999-4012
references.pmid: 25245380
references.citation: J Bioenerg Biomembr. 2010 Apr;42(2):135-42
references.pmid: 20300811
references.citation: Dev Biol. 2011 Feb 15;350(2):290-300
references.pmid: 21145317
references.citation: Development. 2003 Apr;130(8):1579-90
references.pmid: 12620983
references.citation: J Biol Chem. 2014 Oct 17;289(42):29285-96
references.pmid: 25187518
references.citation: Biol Reprod. 2010 Dec;83(6):909-18
references.pmid: 20686180
references.citation: Biol Reprod. 2007 Nov;77(5):872-9
references.pmid: 17625112
references.citation: Mol Cell Biol. 2004 Jun;24(11):4909-19
references.pmid: 15143183
references.citation: Elife. 2013 Apr 16;2:e00415
references.pmid: 23599892
references.citation: Dev Biol. 1977 Nov;61(1):70-8
references.pmid: 411706
references.citation: J Bioenerg Biomembr. 1994 Oct;26(5):495-508
references.pmid: 7896765
references.citation: J Electron Microsc Tech. 1990 Nov;16(3):175-201
references.pmid: 2243277
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6382-9
references.pmid: 22421435
references.citation: Mol Reprod Dev. 2001 Mar;58(3):348-55
references.pmid: 11170277
references.citation: Dev Biol. 1984 Oct;105(2):404-14
references.pmid: 6479445
references.citation: Curr Oncol. 2010 Oct;17(5):6-11
references.pmid: 20975872
references.citation: Curr Biol. 1998 Feb 12;8(4):243-6
references.pmid: 9501989
references.citation: Protein Cell. 2014 Oct;5(10):737-49
references.pmid: 25073422
references.citation: Biochem Soc Trans. 2008 Oct;36(Pt 5):976-80
references.pmid: 18793173
references.citation: Dev Biol. 2005 Oct 15;286(2):493-506
references.pmid: 16168984
references.citation: Cell Metab. 2011 Feb 2;13(2):139-48
references.pmid: 21284981
references.citation: Proc Biol Sci. 2009 Nov 7;276(1674):3799-807
references.pmid: 19692410
references.citation: Reprod Biomed Online. 2014 Jun;28(6):669-83
references.pmid: 24768413
references.citation: Trends Cell Biol. 2015 Mar;25(3):158-70
references.pmid: 25499735
references.citation: Cell Death Differ. 2009 Oct;16(10):1362-71
references.pmid: 19557011
references.citation: Curr Top Dev Biol. 2007;77:21-49
references.pmid: 17222699
references.citation: J Assist Reprod Genet. 2012 Nov;29(11):1227-39
references.pmid: 22976427
references.citation: Nature. 1995 Dec 21-28;378(6559):785-9
references.pmid: 8524413
references.citation: Dev Biol. 2006 Oct 1;298(1):225-33
references.pmid: 16872595