CUL3 induces mitochondrial dysfunction via MRPL12 ubiquitination in renal tubular epithelial cells.
Cullin3
MRPL12
diabetic kidney disease
mitochondrial dysfunction
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
revised:
09
05
2023
received:
26
10
2022
accepted:
31
07
2023
pubmed:
1
8
2023
medline:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide and the strongest predictor of mortality in patients with diabetes. Despite its significance, the pathological mechanism underlying the onset and progression of DKD remains incompletely understood. In this study, we have shown that mitochondrial ribosomal protein L12 (MRPL12) plays a significant role in DKD by modulating mitochondrial function. We demonstrated that MRPL12 was mainly ubiquitinated at K150 in renal tubular epithelial cells. We have found that Cullin3 (CUL3), an E3 ubiquitin ligase, directly interacts with MRPL12 and induces the K63-linked ubiquitination of MRPL12, resulting in mitochondrial biosynthesis dysfunction. Moreover, under high-glucose (HG) conditions in renal tubular epithelial cells, we observed up-regulation of CUL3 expression, significant increase in CUL3-mediated ubiquitination of MRPL12 and dysregulation of mitochondrial biosynthesis. Notably, CUL3 knockdown stabilised the MRPL12 protein and protected mitochondrial biosynthesis under HG conditions. Our findings provide novel insight into how CUL3 affects mitochondrial biosynthesis in renal tubular epithelial cells through MRPL12 ubiquitination and suggest a potential therapeutic strategy for DKD in the future.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5340-5352Subventions
Organisme : "Evergreen tree" Excellent Young and middle-aged Doctors Training Project of Central Hospital Affiliated to Shandong First Medical University
ID : GDRC2021002
Organisme : Jinan Key Laboratory of Medical Sciences Foundation
ID : 20211201
Organisme : Jinan Science and Technology Plan Project
ID : 202134046
Organisme : Jinan Science and Technology Plan Project
ID : 202019064
Organisme : National Natural Science Foundation of China
ID : 82271622
Organisme : National Natural Science Foundation of China
ID : 82071569
Organisme : National Natural Science Foundation of China
ID : 82070756
Organisme : National Natural Science Foundation of China
ID : 82102395
Organisme : National Natural Science Foundation of China
ID : 82200049
Organisme : National Natural Science Foundation of China
ID : 83101639
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2021QH083
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2019MH003
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2021ZD35
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2021112500
Organisme : Natural Science Foundation of Shandong Province
ID : ZR202111250039
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2022QH349
Organisme : Natural Science Foundation of Shandong Province
ID : ZR2022QH374
Informations de copyright
© 2023 Federation of European Biochemical Societies.
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