Regulation of UCP1 and Mitochondrial Metabolism in Brown Adipose Tissue by Reversible Succinylation.

Adipose Tissue, Brown / metabolism Animals Energy Metabolism / genetics Gene Expression Regulation Glucose / metabolism Mice Mice, Knockout Mitochondria / genetics Mitochondrial Proteins / genetics Obesity / genetics Proteomics / methods Sirtuins / genetics Succinic Acid / metabolism Thermogenesis / genetics Uncoupling Protein 1 / genetics
UCP1 brown fat mitochondria succinylation thermogenesis

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
16 05 2019
Historique:
received: 24 07 2018
revised: 06 02 2019
accepted: 20 03 2019
pubmed: 20 4 2019
medline: 17 10 2019
entrez: 20 4 2019
Statut: ppublish

Résumé

Brown adipose tissue (BAT) is rich in mitochondria and plays important roles in energy expenditure, thermogenesis, and glucose homeostasis. We find that levels of mitochondrial protein succinylation and malonylation are high in BAT and subject to physiological and genetic regulation. BAT-specific deletion of Sirt5, a mitochondrial desuccinylase and demalonylase, results in dramatic increases in global protein succinylation and malonylation. Mass spectrometry-based quantification of succinylation reveals that Sirt5 regulates the key thermogenic protein in BAT, UCP1. Mutation of the two succinylated lysines in UCP1 to acyl-mimetic glutamine and glutamic acid significantly decreases its stability and activity. The reduced function of UCP1 and other proteins in Sirt5KO BAT results in impaired mitochondria respiration, defective mitophagy, and metabolic inflexibility. Thus, succinylation of UCP1 and other mitochondrial proteins plays an important role in BAT and in regulation of energy homeostasis.

Identifiants

DOI: 10.1016/j.molcel.2019.03.021 PMID: 31000437 PMC: PMC6525068
pubmed: 31000437
pii: S1097-2765(19)30225-4
doi: 10.1016/j.molcel.2019.03.021
pmc: PMC6525068
mid: NIHMS1525475
pii:
doi:

Substances chimiques

Mitochondrial Proteins 0
SIRT5 protein, mouse 0
Uncoupling Protein 1 0
Succinic Acid AB6MNQ6J6L
Sirtuins EC 3.5.1.-
Glucose IY9XDZ35W2

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

844-857.e7

Subventions

Organisme : NIDDK NIH HHS
ID : K01 DK120740
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK085610
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NICHD NIH HHS
ID : T32 HD083185
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK082659
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM051279
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

GuoXiao Wang (G)

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.

Jesse G Meyer (JG)

Buck Institute for Research on Aging, Novato, CA 94945, USA.

Weikang Cai (W)

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.

Samir Softic (S)

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.

Mengyao Ella Li (ME)

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.

Eric Verdin (E)

Buck Institute for Research on Aging, Novato, CA 94945, USA.

Christopher Newgard (C)

Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Departments of Pharmacology and Cancer Biology and Medicine, Duke University Medical Center, Durham, NC 27708, USA.

Birgit Schilling (B)

Buck Institute for Research on Aging, Novato, CA 94945, USA.

C Ronald Kahn (CR)

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: c.ronald.kahn@joslin.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Tissus › Tissu conjonctif › Tissu adipeux › Tissu adipeux brun › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Métabolisme › Métabolisme énergétique › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Sirtuines › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Diacides carboxyliques › Succinates › Acide succinique › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Phénomènes biologiques › Adaptation biologique › Adaptation physiologique › Régulation de la température corporelle › Thermogenèse › Regulation of UCP1 and Mitochondrial...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines mitochondriales › Protéines de transport de la membrane mitochondriale › Protéines de découplage mitochondrial › Protéine-1 de découplage › Regulation of UCP1 and Mitochondrial...