NDUFS4 Regulates Cristae Remodeling in Diabetic Kidney Disease

Authors

Koki Mise
Jianyin Long
Daniel L Galvan
Zengchun Ye
Guizhen Fan
Irina I Serysheva
Travis I Moore
Jun Wada
Paul T Schumacker
Benny H Chang
Farhad R Danesh

Language

English

Publication Date

6-30-2023

Journal

Research Square

DOI

10.1038/s41467-024-46366-w

PMID

38438382

PMCID

PMC10912198

PubMedCentral® Posted Date

3-4-2024

PubMedCentral® Full Text Version

Post-print

Abstract

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 generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice 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 proteins in linking NDUFS4 with improved cristae morphology. Taken together, we discover the central role of NDUFS4 as a powerful regulator of cristae remodeling, respiratory supercomplexes assembly, and mitochondrial ultrastructure

Keywords

Diabetic nephropathy, Mitochondria, Diabetes complications

Comments

This article has been corrected. See Nat Commun. 2024 Apr 8;15:3022.

Published Open-Access

yes

Recommended Citation

Mise, Koki; Long, Jianyin; Galvan, Daniel L; et al., "NDUFS4 Regulates Cristae Remodeling in Diabetic Kidney Disease" (2023). Faculty, Staff and Student Publications. 888.
https://digitalcommons.library.tmc.edu/uthmed_docs/888