NDUFS4 regulates cristae remodeling in diabetic kidney disease.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 Mar 2024
04 Mar 2024
Historique:
received:
19
06
2023
accepted:
22
02
2024
medline:
6
3
2024
pubmed:
5
3
2024
entrez:
4
3
2024
Statut:
epublish
Résumé
The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that conditional male mice with genetic overexpression of Ndufs4 exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify the role of cristae shaping protein STOML2 in linking NDUFS4 with improved cristae morphology. Together, we provide the evidence on the central role of NDUFS4 as a regulator of cristae remodeling and mitochondrial function in kidney podocytes. We propose that targeting NDUFS4 represents a promising approach to slow the progression of DKD.
Identifiants
pubmed: 38438382
doi: 10.1038/s41467-024-46366-w
pii: 10.1038/s41467-024-46366-w
pmc: PMC10912198
doi:
Substances chimiques
Ndufs4 protein, mouse
0
Electron Transport Complex I
EC 7.1.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1965Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK078900
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL143111
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM072804
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK091310
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIH HHS
ID : S10 OD012304
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2024. The Author(s).
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