Selective knockdown of hexokinase 2 in rods leads to age-related photoreceptor degeneration and retinal metabolic remodeling.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
20 10 2020
20 10 2020
Historique:
received:
07
07
2020
accepted:
05
10
2020
entrez:
21
10
2020
pubmed:
22
10
2020
medline:
14
5
2021
Statut:
epublish
Résumé
Photoreceptors, the primary site of phototransduction in the retina, require energy and metabolites to constantly renew their outer segments. They preferentially consume most glucose through aerobic glycolysis despite possessing abundant mitochondria and enzymes for oxidative phosphorylation (OXPHOS). Exactly how photoreceptors balance aerobic glycolysis and mitochondrial OXPHOS to regulate their survival is still unclear. We crossed rhodopsin-Cre mice with hexokinase 2 (HK2)-floxed mice to study the effect of knocking down HK2, the first rate-limiting enzyme in glycolysis, on retinal health and metabolic remodeling. Immunohistochemistry and Western blots were performed to study changes in photoreceptor-specific proteins and key enzymes in glycolysis and the tricarboxylic acid (TCA) cycle. Changes in retinal structure and function were studied by optical coherence tomography and electroretinography. Mass spectrometry was performed to profile changes in
Identifiants
pubmed: 33082308
doi: 10.1038/s41419-020-03103-7
pii: 10.1038/s41419-020-03103-7
pmc: PMC7576789
doi:
Substances chimiques
Mitochondrial Proteins
0
Hexokinase
EC 2.7.1.1
hexokinase 2, mouse
EC 2.7.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
885Subventions
Organisme : NEI NIH HHS
ID : R01 EY026030
Pays : United States
Références
J Biol Chem. 1989 Jan 15;264(2):1115-23
pubmed: 2910846
J Cell Biol. 2003 Nov 10;163(3):457-61
pubmed: 14597775
Control Clin Trials. 1990 Apr;11(2):116-28
pubmed: 2161310
Biochim Biophys Acta. 2006 Feb;1762(2):181-90
pubmed: 16307870
Vis Neurosci. 2002 Jul-Aug;19(4):395-407
pubmed: 12511073
J Biochem. 2009 Oct;146(4):455-61
pubmed: 19666648
Int J Mol Sci. 2019 Feb 11;20(3):
pubmed: 30754662
Biophys J. 1997 May;72(5):1954-62
pubmed: 9129800
Prog Retin Eye Res. 2013 May;34:49-77
pubmed: 23219692
Science. 1976 Dec 3;194(4269):1071-4
pubmed: 982063
J Biol Chem. 2019 Jun 28;294(26):10278-10289
pubmed: 31110046
J Mol Med (Berl). 2013 Aug;91(8):917-27
pubmed: 23873151
Elife. 2017 Sep 13;6:
pubmed: 28901286
Sci Signal. 2009 Nov 17;2(97):ra73
pubmed: 19920251
Cell. 2006 Nov 3;127(3):579-89
pubmed: 17081979
Cell Death Dis. 2020 Jun 4;11(6):422
pubmed: 32499533
Int Rev Cytol. 2000;196:245-313
pubmed: 10730217
Clin Exp Ophthalmol. 2015 May-Jun;43(4):367-76
pubmed: 25330055
Cell Rep. 2018 May 29;23(9):2629-2642
pubmed: 29847794
Mol Vis. 2016 Jul 23;22:847-85
pubmed: 27499608
Biochim Biophys Acta. 2007 Oct;1768(10):2510-5
pubmed: 17617374
J Neurosci. 2012 Nov 7;32(45):15715-27
pubmed: 23136411
Cell Biochem Biophys. 2014 Apr;68(3):475-8
pubmed: 24068518
Nature. 2008 Mar 13;452(7184):181-6
pubmed: 18337815
Biochim Biophys Acta. 2016 Aug;1857(8):1086-1101
pubmed: 26971832
Science. 2002 Mar 8;295(5561):1852-8
pubmed: 11884745
Sci Rep. 2016 Dec 14;6:39161
pubmed: 27966644
Cell Rep. 2019 Jul 30;28(5):1323-1334.e4
pubmed: 31365873
J Neuroinflammation. 2013 Nov 14;10:137
pubmed: 24224958
FASEB J. 1990 Nov;4(14):3224-33
pubmed: 2227213
J Neurosci Res. 2015 Jul;93(7):1079-92
pubmed: 25801286
J Biol Chem. 1967 Apr 10;242(7):1635-45
pubmed: 4225734
Sci Rep. 2016 Nov 24;6:37727
pubmed: 27883057
Prog Retin Eye Res. 2013 Nov;37:114-40
pubmed: 23994436
JCI Insight. 2016 Sep 22;1(15):e86976
pubmed: 27699244
Glia. 2014 Jul;62(7):1110-24
pubmed: 24687761
Science. 2009 May 22;324(5930):1029-33
pubmed: 19460998
Expert Opin Ther Targets. 2013 Oct;17(10):1221-33
pubmed: 23984984
Front Cell Dev Biol. 2020 Apr 30;8:266
pubmed: 32426353
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3530-3535
pubmed: 30808746
Cell Death Dis. 2018 Jul 3;9(7):737
pubmed: 29970877
Redox Biol. 2013 Feb 09;1:258-64
pubmed: 24024159
Arch Biochem Biophys. 2010 Mar 15;495(2):174-81
pubmed: 20097153
Front Mol Neurosci. 2015 Nov 17;8:67
pubmed: 26635520
Invest Ophthalmol Vis Sci. 2012 May 17;53(6):2921-7
pubmed: 22447858
J Neurochem. 2015 Jun;133(6):909-18
pubmed: 25692504
Genesis. 2005 Feb;41(2):73-80
pubmed: 15682388
Elife. 2017 Jun 09;6:
pubmed: 28598329
Front Plant Sci. 2014 Oct 15;5:552
pubmed: 25360142
Sci Rep. 2017 Dec 19;7(1):17863
pubmed: 29259242
Hum Gene Ther. 2019 Dec;30(12):1461-1476
pubmed: 31642343
Invest Ophthalmol Vis Sci. 1997 Dec;38(13):2721-8
pubmed: 9418724
Exp Eye Res. 2019 Jan;178:15-26
pubmed: 30218651
Invest Ophthalmol Vis Sci. 2018 Mar 20;59(4):AMD41-AMD47
pubmed: 30025108
Int J Mol Sci. 2017 Mar 01;18(3):
pubmed: 28257068
Curr Pharm Des. 2006;12(18):2249-70
pubmed: 16787253
Methods Enzymol. 2015;561:149-70
pubmed: 26358904
Science. 1956 Feb 24;123(3191):309-14
pubmed: 13298683
Med Hypotheses. 2019 Sep;130:109263
pubmed: 31383331