RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through the disruption of mitochondrial stability.
Mitochondrion
; 75: 101851, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38336146
ABSTRACT
Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Mitocondriales
/
Lesión Renal Aguda
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mitochondrion
Año:
2024
Tipo del documento:
Article