Dataset Information

Facultative protein selenation controls redox sensitivity, adipose tissue thermogenesis and obesity

ABSTRACT: Oxidation of cysteines by reactive oxygen species (ROS) initiates thermogenesis in brown and beige adipose tissues. Cellular selenols, where sulfur is replaced with selenium, exhibit enhanced reactivity with ROS. Here we developed a mass spectrometric method to interrogate incorporation of selenols into proteins. Unexpectedly, this approach revealed facultative incorporation of selenium into proteins that lack canonical encoding for selenium-containing amino acids. Selenium was selectively incorporated into regulatory sites on key metabolic proteins, including as selenocysteine replacing cysteine at position 253 in UCP1. 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brown Adipose Tissue

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: mark Jedrychowski

LAB HEAD: Edward Chouchani

PROVIDER: PXD018225 | Pride | 2021-09-09

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	289097_JM01444EC_MPJ_BATcells_selenomethioine_treatment_1_2017.mzIdentML	Mzid
	289098_JM01439EC_MPJ_BATcells_selenomethioine_treatment_1_2017.mzIdentML	Mzid
	289099_JM01440EC_MPJ_BATcells_selenomethioine_treatment_1_2017.mzIdentML	Mzid
	289100_JM01441EC_MPJ_BATcells_selenomethioine_treatment_1_2017.mzIdentML	Mzid
	289102_JM01443EC_MPJ_BATcells_selenomethioine_treatment_1_2017.mzIdentML	Mzid

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Publications

Facultative protein selenation regulates redox sensitivity, adipose tissue thermogenesis, and obesity.

Jedrychowski Mark P MP Lu Gina Z GZ Szpyt John J Mariotti Marco M Garrity Ryan R Paulo Joao A JA Schweppe Devin K DK Laznik-Bogoslavski Dina D Kazak Lawrence L Murphy Michael P MP Gladyshev Vadim N VN Gygi Steven P SP Chouchani Edward T ET Spiegelman Bruce M BM

Proceedings of the National Academy of Sciences of the United States of America 20200501 20

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 rev ...[more]

PMID: 32358195

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