Briones-Herrera 2020 Free Radic Biol Med
|Briones-Herrera A, Ramírez-Camacho I, Zazueta C, Tapia E, Pedraza-Chaverri J (2020) Altered proximal tubule fatty acid utilization, mitophagy, fission and supercomplexes arrangement in experimental Fanconi syndrome are ameliorated by sulforaphane-induced mitochondrial biogenesis. Free Radic Biol Med 153:54-70.|
Abstract: The kidney proximal tubule function relies on oxidative phosphorylation (OXPHOS), thus mitochondrial dysfunction is characteristic of acute kidney injury (AKI). Maleic acid (MA) can induce an experimental model of Fanconi syndrome that is associated to oxidative stress and decreased oxygen consumption. Sulforaphane (SF) is an antioxidant known to protect against MA-induced AKI. The molecular basis by which SF maintains the bioenergetics in MA-induced AKI is not fully understood. To achieve it, rats were submitted to a protective scheme: SF (1 mg/kg/day i.p.) for four days and, at the fourth day, they received a single dose of MA (400 mg/kg i.p.), getting four main experimental groups: (1) control (CT), (2) MA-nephropathy (MA), (3) SF-protected and (4) SF-control (SF). Additionally, a similar protective schema was tested in cultured NRK-52E cells with different concentrations of SF and MA. In the animal model, SF prevented the MA-induced alterations: decrease in fatty acid-related oxygen consumption rate, OXPHOS capacity, mitochondrial membrane potential (Ψmt), and the activity of complex I (CI) as its monomeric and supercomplexes forms; the antioxidant also increased the activity of cytochrome c oxidase as well as mitochondrial biogenesis markers. Thus, SF prevented the MA-induced increase in fission, mitophagy and autophagy markers. In NRK-52E cells, we found that SF prevented the MA-induced cell death, increased mitochondrial mass and ameliorated the loss of Ψmt. We concluded that SF-induced biogenesis protects against mitochondrial dysfunction maintaining Ψmt, activities of mitochondrial complexes and supercomplexes, and prevents the extensive fission and mitophagy.
Copyright © 2020 Elsevier Inc. All rights reserved.
• Keywords: Acute kidney injury, Bioenergetics, Maleic acid, Mitochondria, Mitochondrial biogenesis, Mitochondrial homeostasis, Mitochondrial membrane potential, Mitochondrial supercomplexes, Mitophagy, Sulforaphane • Bioblast editor: Plangger M • O2k-Network Lab: MX Mexico City Pedraza Chaverri J
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, Pharmacology;toxicology
Organism: Rat Tissue;cell: Kidney Preparation: Isolated mitochondria Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex
Coupling state: LEAK, OXPHOS Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k