Reprograming of proteasomal degradation by branched chain amino acid metabolism.
Caenorhabditis elegans
aging
branched-chain amino acid
branched-chain aminotransferase
metabolism
proteasome
proteostasis
ubiquitin
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
revised:
03
08
2022
received:
12
04
2022
accepted:
09
09
2022
pubmed:
29
9
2022
medline:
15
12
2022
entrez:
28
9
2022
Statut:
ppublish
Résumé
Branched-chain amino acid (BCAA) metabolism is a central hub for energy production and regulation of numerous physiological processes. Controversially, both increased and decreased levels of BCAAs are associated with longevity. Using genetics and multi-omics analyses in Caenorhabditis elegans, we identified adaptive regulation of the ubiquitin-proteasome system (UPS) in response to defective BCAA catabolic reactions after the initial transamination step. Worms with impaired BCAA metabolism show a slower turnover of a GFP-based proteasome substrate, which is suppressed by loss-of-function of the first BCAA catabolic enzyme, the branched-chain aminotransferase BCAT-1. The exogenous supply of BCAA-derived carboxylic acids, which are known to accumulate in the body fluid of patients with BCAA metabolic disorders, is sufficient to regulate the UPS. The link between BCAA intermediates and UPS function presented here sheds light on the unexplained role of BCAAs in the aging process and opens future possibilities for therapeutic interventions.
Identifiants
pubmed: 36168305
doi: 10.1111/acel.13725
pmc: PMC9741504
doi:
Substances chimiques
Proteasome Endopeptidase Complex
EC 3.4.25.1
Amino Acids, Branched-Chain
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13725Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : EXC 2030 - 390661388
Organisme : Deutsche Forschungsgemeinschaft
ID : FKZ: ZUK81/1
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1218
Organisme : Alexander von Humboldt Foundation
Informations de copyright
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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