PMID- 34175439 OWN - NLM STAT- MEDLINE DCOM- 20210826 LR - 20210826 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 172 DP - 2021 Aug 20 TI - Temporal characterization of mitochondrial impairment in the unilateral ureteral obstruction model in rats. PG - 358-371 LID - S0891-5849(21)00384-1 [pii] LID - 10.1016/j.freeradbiomed.2021.06.019 [doi] AB - 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 gamma co-activator-1alpha (PGC-1alpha), 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Jimenez-Uribe, Alexis Paulina AU - Jimenez-Uribe AP AD - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de Mexico, CDMX 04510, Mexico. FAU - Bellido, Belen AU - Bellido B AD - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de Mexico, CDMX 04510, Mexico. FAU - Aparicio-Trejo, Omar Emiliano AU - Aparicio-Trejo OE AD - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de Mexico, CDMX 04510, Mexico. FAU - Tapia, Edilia AU - Tapia E AD - Departmento de Patofisiologia Cardio-renal, Instituto Nacional de Cardiologia "Ignacio Chavez", Mexico City 14080, Mexico. FAU - Sanchez-Lozada, Laura Gabriela AU - Sanchez-Lozada LG AD - Departmento de Patofisiologia Cardio-renal, Instituto Nacional de Cardiologia "Ignacio Chavez", Mexico City 14080, Mexico. FAU - Hernandez-Santos, Jose Antonio AU - Hernandez-Santos JA AD - Laboratorio de Neurobiologia Molecular y Celular, Instituto Nacional de Neurologia y Neurocirugia, Manuel Velasco Suarez, Av. Insurgentes Sur # 3877, La Fama, Alcaldia Tlalpan, CP 14269, Ciudad de Mexico, Mexico. FAU - Fernandez-Valverde, Francisca AU - Fernandez-Valverde F AD - Laboratorio de Patologia Experimental, Instituto Nacional de Neurologia y Neurocirugia, Manuel Velasco Suarez, Av. Insurgentes Sur # 3877, La Fama, Alcaldia Tlalpan, CP 14269, Ciudad de Mexico, Mexico. FAU - Hernandez-Cruz, Estefani Yaquelin AU - Hernandez-Cruz EY AD - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de Mexico, CDMX 04510, Mexico. FAU - Orozco-Ibarra, Marisol AU - Orozco-Ibarra M AD - Laboratorio de Neurobiologia Molecular y Celular, Instituto Nacional de Neurologia y Neurocirugia, Manuel Velasco Suarez, Av. Insurgentes Sur # 3877, La Fama, Alcaldia Tlalpan, CP 14269, Ciudad de Mexico, Mexico. FAU - Pedraza-Chaverri, Jose AU - Pedraza-Chaverri J AD - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de Mexico, CDMX 04510, Mexico. Electronic address: pedraza@unam.mx. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210624 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 SB - IM MH - Animals MH - Fibrosis MH - Mitochondria MH - Mitophagy MH - Organelle Biogenesis MH - Rats MH - *Ureteral Obstruction OTO - NOTNLM OT - Mitochondrial bioenergetics alterations OT - Mitochondrial biogenesis OT - Mitochondrial dysfunction OT - Mitophagy OT - Renal fibrosis OT - Unilateral ureteral obstruction EDAT- 2021/06/28 06:00 MHDA- 2021/08/27 06:00 CRDT- 2021/06/27 20:42 PHST- 2021/05/05 00:00 [received] PHST- 2021/05/31 00:00 [revised] PHST- 2021/06/21 00:00 [accepted] PHST- 2021/06/28 06:00 [pubmed] PHST- 2021/08/27 06:00 [medline] PHST- 2021/06/27 20:42 [entrez] AID - S0891-5849(21)00384-1 [pii] AID - 10.1016/j.freeradbiomed.2021.06.019 [doi] PST - ppublish SO - Free Radic Biol Med. 2021 Aug 20;172:358-371. doi: 10.1016/j.freeradbiomed.2021.06.019. Epub 2021 Jun 24.