Jimenez-Uribe 2021 Free Radic Biol Med
| Jimenez-Uribe AP, Bellido B, Aparicio-Trejo OE, Tapia E, Sanchez-Lozada LG, Hernandez-Santos JA, Fernandez-Valverde F, Hernandez-Cruz EY, Orozco-Ibarra M, Pedraza-Chaverri J (2021) Temporal characterization of mitochondrial impairment in the unilateral ureteral obstruction model in rats. Free Radic Biol Med 172:358-71. |
Jimenez-Uribe Alexis Paulina, Bellido Belen, Aparicio-Trejo Omar Emiliano, Tapia Edilia, Sanchez-Lozada Laura Gabriela, Hernandez-Santos Jose Antonio, Fernandez-Valverde Francisca, Hernandez-Cruz Estefani Yaquelin, Orozco-Ibarra Marisol, Pedraza-Chaverri Jose (2021) Free Radic Biol Med
Abstract: Renal fibrosis is a well-known mechanism that favors chronic kidney disease (CKD) development in obstructive nephropathy, a significant pathology worldwide. Fibrosis induction involves several pathways, and although mitochondrial alterations have recently emerged as a critical factor that triggers renal damage in the obstructed kidney, the temporal mitochondrial alterations during the fibrotic induction remain unexplored. Therefore, in this work, we evaluated the time course of mitochondrial mass and bioenergetics alterations induced by a unilateral ureteral obstruction (UUO), a widely used model to study the mechanism involved in kidney fibrosis induction and progression. Our results show a marked reduction in mitochondrial oxidative phosphorylation (OXPHOS) in the obstructed kidney on days 7 to 28 of obstruction without significant mitochondrial coupling changes. Besides, we observed that mitochondrial mass was reduced, probably due to decreased biogenesis and mitophagy induction. OXPHOS impairment was associated with decreased mitochondrial biogenesis markers, the peroxisome proliferator-activated receptor γ co-activator-1alpha (PGC-1α), and nuclear respiratory factor 1 (NRF1); and also, with the induction of mitophagy in a PTEN-induced kinase 1 (PINK1) and Parkin independent way. It is concluded that the impairment of OXPHOS capacity may be explained by the reduction in mitochondrial biogenesis and the induction of mitophagy during fibrotic progression. • Keywords: Mitochondrial bioenergetics alterations, Mitochondrial biogenesis, Mitochondrial dysfunction, Mitophagy, Renal fibrosis, Unilateral ureteral obstruction • Bioblast editor: Reiswig R • O2k-Network Lab: MX Mexico City Pedraza Chaverri J
Labels: MiParea: Respiration, mt-Biogenesis;mt-density
Pathology: Other
Organism: Rat Tissue;cell: Kidney Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS
Pathway: N, S, ROX
HRR: Oxygraph-2k
