Facultative protein selenation regulates redox sensitivity, adipose tissue thermogenesis, and obesity.
ROS
brown adipose tissue
cysteine
selenocysteine
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
19 05 2020
19 05 2020
Historique:
pubmed:
3
5
2020
medline:
11
8
2020
entrez:
3
5
2020
Statut:
ppublish
Résumé
Oxidation of cysteine thiols by physiological reactive oxygen species (ROS) initiates thermogenesis in brown and beige adipose tissues. Cellular selenocysteines, where sulfur is replaced with selenium, exhibit enhanced reactivity with ROS. Despite their critical roles in physiology, methods for broad and direct detection of proteogenic selenocysteines are limited. Here we developed a mass spectrometric method to interrogate incorporation of selenium into proteins. Unexpectedly, this approach revealed facultative incorporation of selenium as selenocysteine or selenomethionine into proteins that lack canonical encoding for selenocysteine. Selenium was selectively incorporated into regulatory sites on key metabolic proteins, including as selenocysteine-replacing cysteine at position 253 in uncoupling protein 1 (UCP1). This facultative utilization of selenium was initiated by increasing cellular levels of organic, but not inorganic, forms of selenium. Remarkably, dietary selenium supplementation elevated facultative incorporation into UCP1, elevated energy expenditure through thermogenic adipose tissue, and protected against obesity. Together, these findings reveal the existence of facultative protein selenation, which correlates with impacts on thermogenic adipocyte function and presumably other biological processes as well.
Identifiants
pubmed: 32358195
pii: 2001387117
doi: 10.1073/pnas.2001387117
pmc: PMC7245117
doi:
Substances chimiques
Reactive Oxygen Species
0
Ucp1 protein, mouse
0
Uncoupling Protein 1
0
Selenium
H6241UJ22B
Cysteine
K848JZ4886
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
10789-10796Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK123095
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117149
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA080946
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00015/3
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM132129
Pays : United States
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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