Electron Transport Chain Complex II Regulates Steroid Metabolism.
Biochemistry
Biological Sciences
Molecular Biology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
24 Jul 2020
24 Jul 2020
Historique:
received:
07
01
2020
revised:
23
04
2020
accepted:
15
06
2020
pubmed:
6
7
2020
medline:
6
7
2020
entrez:
6
7
2020
Statut:
ppublish
Résumé
The first steroidogenic enzyme, cytochrome P450-side-chain-cleavage (SCC), requires electron transport chain (ETC) complexes III and IV to initiate steroid metabolic processes for mammalian survival. ETC complex II, containing succinate dehydrogenase (quinone), acts with the TCA cycle and has no proton pumping capacity. We show that complex II is required for SCC activation through the proton pump, generating an intermediate state for addition of phosphate by succinate. Phosphate anions in the presence of succinate form a stable mitochondrial complex with higher enthalpy (-ΔH) and enhanced activity. Inhibition of succinate action prevents SCC processing at the intermediate state and ablates activity and mitochondrial protein network. This is the first report directly showing that a protein intermediate state is activated by succinate, facilitating the ETC complex II to interact with complexes III and IV for continued mitochondrial metabolic process, suggesting complex II is essential for steroid metabolism regulation.
Identifiants
pubmed: 32623340
pii: S2589-0042(20)30482-X
doi: 10.1016/j.isci.2020.101295
pmc: PMC7334606
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101295Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare that they do not have any conflicts of interest. They also declare that they do not have any financial interests.
Références
N Engl J Med. 1996 Dec 19;335(25):1870-8
pubmed: 8948562
Endocrinology. 2016 Mar;157(3):1222-33
pubmed: 26697723
J Biol Chem. 1998 Aug 7;273(32):20596-602
pubmed: 9685417
Endocr Rev. 2011 Feb;32(1):81-151
pubmed: 21051590
J Biol Chem. 1979 Aug 10;254(15):7255-64
pubmed: 222762
Mol Cell. 2016 Jul 7;63(1):21-33
pubmed: 27345149
Trends Endocrinol Metab. 2017 Nov;28(11):771-793
pubmed: 29031608
Mol Cell. 2008 Oct 10;32(1):32-42
pubmed: 18851831
Science. 1992 Jun 26;256(5065):1815-7
pubmed: 1615327
Trends Cell Biol. 2009 Feb;19(2):81-8
pubmed: 19144519
Nature. 2012 Nov 15;491(7424):374-83
pubmed: 23151580
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7250-5
pubmed: 10377400
Nat Rev Mol Cell Biol. 2018 Feb;19(2):77-92
pubmed: 28792006
J Mol Biol. 1999 Jun 18;289(4):981-90
pubmed: 10369776
Proc Natl Acad Sci U S A. 1986 Dec;83(23):8962-6
pubmed: 3024157
J Mol Biol. 1996 May 24;258(5):707-25
pubmed: 8637003
Am J Physiol. 1988 Dec;255(6 Pt 2):F1170-7
pubmed: 3202180
Mol Cell Biol. 2018 Dec 11;39(1):
pubmed: 30348838
Nature. 2004 May 13;429(6988):188-93
pubmed: 15141213
Cell. 1987 Jun 5;49(5):651-8
pubmed: 3034431
Cell. 1985 Nov;43(1):339-50
pubmed: 2866845
Oncotarget. 2017 Jul 12;8(56):96351-96358
pubmed: 29221211
Nat Commun. 2017 May 31;8:15621
pubmed: 28561074
J Steroid Biochem Mol Biol. 1992 Dec;43(8):779-804
pubmed: 22217824
J Biol Chem. 2005 Jul 1;280(26):25103-10
pubmed: 15870080
Sci Adv. 2017 Feb 24;3(2):e1602038
pubmed: 28275724
Endocrinol Diabetes Metab Case Rep. 2016;2016:
pubmed: 27855232
J Biol Chem. 2008 Apr 4;283(14):8837-45
pubmed: 18250166
J Lipid Res. 2011 Dec;52(12):2111-35
pubmed: 21976778
J Biol Chem. 1993 Aug 15;268(23):17126-30
pubmed: 8349601
J Steroid Biochem Mol Biol. 2017 Jan;165(Pt A):18-37
pubmed: 26960203
Am J Ophthalmol. 2012 May;153(5):896-902.e1
pubmed: 22265145
Trends Biochem Sci. 1997 Apr;22(4):118-23
pubmed: 9149530
Annu Rev Biochem. 2007;76:723-49
pubmed: 17263664