Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 04 2024
30 04 2024
Historique:
received:
18
12
2023
accepted:
18
04
2024
medline:
1
5
2024
pubmed:
1
5
2024
entrez:
30
4
2024
Statut:
epublish
Résumé
Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.
Identifiants
pubmed: 38688959
doi: 10.1038/s41598-024-60030-9
pii: 10.1038/s41598-024-60030-9
doi:
Substances chimiques
Protease La
EC 3.4.21.53
Polyphosphates
0
Tyrosine
42HK56048U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9923Subventions
Organisme : Grantová Agentura České Republiky
ID : 894 Grant No. 1825144Y
Organisme : Grantová Agentura České Republiky
ID : 894 Grant No. 1825144Y
Organisme : Grantová Agentura České Republiky
ID : 894 Grant No. 1825144Y
Organisme : Interreg
ID : StruBioMol, ITMS: 305011X666
Organisme : Interreg
ID : StruBioMol, ITMS: 305011X666
Organisme : Interreg
ID : StruBioMol, ITMS: 305011X666
Organisme : Interreg
ID : StruBioMol, ITMS: 305011X666
Organisme : Interreg
ID : StruBioMol, ITMS: 305011X666
Organisme : European Regional Development Fund, European Union
ID : UP CIISB (No. CZ.02.1.01/0.0/0.0/18_046/0015974)
Organisme : European Regional Development Fund, European Union
ID : UP CIISB (No. CZ.02.1.01/0.0/0.0/18_046/0015974)
Organisme : European Regional Development Fund
ID : BIOMEDIRES - II. stage, ITMS: 313011W428
Organisme : Agentúra na Podporu Výskumu a Vývoja
ID : APVV-15-0375, APVV-19-0298
Organisme : Agentúra na Podporu Výskumu a Vývoja
ID : APVV-15-0375, APVV-19-0298
Organisme : Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
ID : 2/0069/23
Organisme : Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
ID : 2/0069/23
Informations de copyright
© 2024. The Author(s).
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