β-carotene oxygenase 2 deficiency-triggered mitochondrial oxidative stress promotes low-grade inflammation and metabolic dysfunction.
Diabetes
Human
Macrophage
Mitochondrial respiratory supercomplex assembly
Natural killer cell
Superoxide
Journal
Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159
Informations de publication
Date de publication:
20 02 2021
20 02 2021
Historique:
received:
14
09
2020
revised:
30
12
2020
accepted:
03
01
2021
pubmed:
17
1
2021
medline:
25
6
2021
entrez:
16
1
2021
Statut:
ppublish
Résumé
Low-grade inflammation is a critical pathological factor contributing to the development of metabolic disorders. β-carotene oxygenase 2 (BCO2) was initially identified as an enzyme catalyzing carotenoids in the inner mitochondrial membrane. Mutations in BCO2 are associated with inflammation and metabolic disorders in humans, yet the underlying mechanisms remain unknown. Here, we used loss-of-function approaches in mice and cell culture models to investigate the role of BCO2 in inflammation and metabolic dysfunction. We demonstrated decreases in BCO2 mRNA and protein levels and suppression of mitochondrial respiratory complex I proteins and mitochondrial superoxide dismutase levels in the liver of type 2 diabetic human subjects. Deficiency of BCO2 caused disruption of assembly of the mitochondrial respiratory supercomplexes, such as supercomplex III
Identifiants
pubmed: 33453359
pii: S0891-5849(21)00009-5
doi: 10.1016/j.freeradbiomed.2021.01.003
pmc: PMC7946548
mid: NIHMS1662690
pii:
doi:
Substances chimiques
beta Carotene
01YAE03M7J
Dioxygenases
EC 1.13.11.-
Bco2 protein, mouse
EC 1.14.99.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
271-284Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103648
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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