Progressive Reduction in Mitochondrial Mass Is Triggered by Alterations in Mitochondrial Biogenesis and Dynamics in Chronic Kidney Disease Induced by 5/6 Nephrectomy
Rodrigo Prieto-Carrasco,
Fernando E. García-Arroyo,
Omar Emiliano Aparicio-Trejo,
Pedro Rojas-Morales,
Juan Carlos León-Contreras,
Rogelio Hernández-Pando,
Laura Gabriela Sánchez-Lozada,
Edilia Tapia,
José Pedraza-Chaverri
Affiliations
Rodrigo Prieto-Carrasco
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico
Fernando E. García-Arroyo
Department of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
Omar Emiliano Aparicio-Trejo
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico
Pedro Rojas-Morales
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico
Juan Carlos León-Contreras
Experimental Pathology Section, National Institute of Medical Sciences and Nutrition “Salvador Zubirán”, Mexico City 14000, Mexico
Rogelio Hernández-Pando
Experimental Pathology Section, National Institute of Medical Sciences and Nutrition “Salvador Zubirán”, Mexico City 14000, Mexico
Laura Gabriela Sánchez-Lozada
Department of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
Edilia Tapia
Department of Cardio-Renal Pathophysiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City 14080, Mexico
José Pedraza-Chaverri
Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico
The five-sixth nephrectomy (5/6Nx) model is widely used to study the mechanisms involved in chronic kidney disease (CKD) progression. Mitochondrial impairment is a critical mechanism that favors CKD progression. However, until now, there are no temporal studies of the change in mitochondrial biogenesis and dynamics that allow determining the role of these processes in mitochondrial impairment and renal damage progression in the 5/6Nx model. In this work, we determined the changes in mitochondrial biogenesis and dynamics markers in remnant renal mass from days 2 to 28 after 5/6Nx. Our results show a progressive reduction in mitochondrial biogenesis triggered by reducing two principal regulators of mitochondrial protein expression, the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and the peroxisome proliferator-activated receptor alpha. Furthermore, the reduction in mitochondrial biogenesis proteins strongly correlates with the increase in renal damage markers. Additionally, we found a slow and gradual change in mitochondrial dynamics from fusion to fission, favoring mitochondrial fragmentation at later stages after 5/6Nx. Together, our results suggest that 5/6Nx induces the progressive reduction in mitochondrial mass over time via the decrease in mitochondrial biogenesis factors and a slow shift from mitochondrial fission to fusion; both mechanisms favor CKD progression in the remnant renal mass.
