Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
16 05 2022
16 05 2022
Historique:
received:
09
09
2020
accepted:
23
04
2022
entrez:
16
5
2022
pubmed:
17
5
2022
medline:
20
5
2022
Statut:
epublish
Résumé
Mitochondrial dysfunction is a key driver of diabetes and other metabolic diseases. Mitochondrial redox state is highly impactful to metabolic function but the mechanism driving this is unclear. We generated a transgenic mouse which overexpressed the redox enzyme Thioredoxin Reductase 2 (TrxR2), the rate limiting enzyme in the mitochondrial thioredoxin system. We found augmentation of TrxR2 to enhance metabolism in mice under a normal diet and to increase resistance to high-fat diet induced metabolic dysfunction by both increasing glucose tolerance and decreasing fat deposition. We show this to be caused by increased mitochondrial function which is driven at least in part by enhancements to the tricarboxylic acid cycle and electron transport chain function. Our findings demonstrate a role for TrxR2 and mitochondrial thioredoxin as metabolic regulators and show a critical role for redox enzymes in controlling functionality of key mitochondrial metabolic systems.
Identifiants
pubmed: 35577894
doi: 10.1038/s42003-022-03405-w
pii: 10.1038/s42003-022-03405-w
pmc: PMC9110405
doi:
Substances chimiques
Thioredoxin Reductase 2
EC 1.8.1.9
Thioredoxins
52500-60-4
Txnrd2 protein, mouse
EC 1.8.1.9
Banques de données
Dryad
['10.5061/dryad.fttdz08vk']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
467Subventions
Organisme : NIMH NIH HHS
ID : R01 MH121928
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG061051
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG065301
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079626
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Mol Cell Biol. 2005 Mar;25(5):1980-8
pubmed: 15713651
Biochim Biophys Acta. 2008 Nov;1780(11):1273-90
pubmed: 18267127
J Biol Chem. 1989 Aug 25;264(24):13963-6
pubmed: 2668278
Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R927-35
pubmed: 16675629
Methods Mol Biol. 2013;1005:181-97
pubmed: 23606258
Cancers (Basel). 2010 Mar 25;2(2):209-32
pubmed: 24281068
Biochem J. 2013 Oct 15;455(2):157-67
pubmed: 23924350
Free Radic Biol Med. 2000 Aug;29(3-4):222-30
pubmed: 11035250
Anal Biochem. 1997 Oct 1;252(1):153-9
pubmed: 9324953
Nutrients. 2019 Oct 25;11(11):
pubmed: 31731503
Physiol Res. 2005;54(1):67-72
pubmed: 15717843
Science. 1992 May 1;256(5057):628-32
pubmed: 1533953
Cell Metab. 2010 Dec 1;12(6):668-74
pubmed: 21109199
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5860-5
pubmed: 8650183
EMBO J. 1998 May 1;17(9):2596-606
pubmed: 9564042
Aging Cell. 2008 Dec;7(6):866-78
pubmed: 18778410
Endocr Rev. 2010 Jun;31(3):364-95
pubmed: 20156986
Aging Cell. 2017 Aug;16(4):683-692
pubmed: 28474396
Prev Chronic Dis. 2017 Mar 16;14:E24
pubmed: 28301314
Integr Med (Encinitas). 2014 Aug;13(4):35-43
pubmed: 26770107
Biochem J. 2000 Feb 15;346 Pt 1:1-8
pubmed: 10657232
Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1392-400
pubmed: 25646482