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Foxp3 drives oxidative phosphorylation and protection from lipotoxicity.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Foxp3 drives oxidative phosphorylation and protection from lipotoxicity.
Συγγραφείς: Howie D; Sir William Dunn School of Pathology., Cobbold SP; Sir William Dunn School of Pathology., Adams E; Sir William Dunn School of Pathology., Ten Bokum A; Sir William Dunn School of Pathology., Necula AS; Sir William Dunn School of Pathology., Zhang W; Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital., Huang H; Radcliffe Department of Medicine, John Radcliffe Hospital., Roberts DJ; Radcliffe Department of Medicine, John Radcliffe Hospital.; National Health Service Blood and Transplant, John Radcliffe Hospital, University of Oxford, Oxford, England, United Kingdom., Thomas B; Sir William Dunn School of Pathology., Hester SS; Sir William Dunn School of Pathology., Vaux DJ; Sir William Dunn School of Pathology., Betz AG; Sir William Dunn School of Pathology., Waldmann H; Sir William Dunn School of Pathology.
Πηγή: JCI insight [JCI Insight] 2017 Feb 09; Vol. 2 (3), pp. e89160. Date of Electronic Publication: 2017 Feb 09.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Print ISSN: 2379-3708 (Print) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE
Imprint Name(s): Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-
Ιατρικοί όροι (MeSH): Fatty Acids/*metabolism , Forkhead Transcription Factors/*metabolism , Proteomics/*methods , T-Lymphocytes, Regulatory/*metabolism, Adenosine Triphosphate/metabolism ; Cell Nucleus/metabolism ; Female ; Humans ; Lipid Metabolism ; Mass Spectrometry ; Oxidative Phosphorylation ; Up-Regulation
Περίληψη: Tregs can adopt a catabolic metabolic program with increased capacity for fatty acid oxidation-fueled oxidative phosphorylation (OXPHOS). It is unclear why this form of metabolism is favored in Tregs and, more specifically, whether this program represents an adaptation to the environment and developmental cues or is "hardwired" by Foxp3. Here we show, using metabolic analysis and an unbiased mass spectroscopy-based proteomics approach, that Foxp3 is both necessary and sufficient to program Treg-increased respiratory capacity and Tregs' increased ability to utilize fatty acids to fuel oxidative phosphorylation. Foxp3 drives upregulation of components of all the electron transport complexes, increasing their activity and ATP generation by oxidative phosphorylation. Increased fatty acid β-oxidation also results in selective protection of Foxp3+ cells from fatty acid-induced cell death. This observation may provide novel targets for modulating Treg function or selection therapeutically.
Competing Interests: The authors declare that no conflict of interest exists.
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Grant Information: RP-PG-0310-1003 United Kingdom DH_ Department of Health; RP-PG-0310-1004 United Kingdom DH_ Department of Health; G1000215 United Kingdom MRC_ Medical Research Council
Substance Nomenclature: 0 (FOXP3 protein, human)
0 (Fatty Acids)
0 (Forkhead Transcription Factors)
0 (Foxp3 protein, mouse)
8L70Q75FXE (Adenosine Triphosphate)
Entry Date(s): Date Created: 20170215 Date Completed: 20190621 Latest Revision: 20250530
Update Code: 20260130
PubMed Central ID: PMC5291728
DOI: 10.1172/jci.insight.89160
PMID: 28194435
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2379-3708
DOI:10.1172/jci.insight.89160