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The targeted anti-oxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue.
Gottwald, Esther M; Duss, Michael; Bugarski, Milica; Haenni, Dominik; Schuh, Claus D; Landau, Ehud M; Hall, Andrew M.
Afiliação
  • Gottwald EM; Institute of Anatomy, University of Zurich, Zurich, Switzerland.
  • Duss M; Department of Chemistry, University of Zurich, Zurich, Switzerland.
  • Bugarski M; Institute of Anatomy, University of Zurich, Zurich, Switzerland.
  • Haenni D; Institute of Anatomy, University of Zurich, Zurich, Switzerland.
  • Schuh CD; Center for Microscopy and Image Analysis, University of Zurich, Zurich, Switzerland.
  • Landau EM; Institute of Anatomy, University of Zurich, Zurich, Switzerland.
  • Hall AM; Department of Chemistry, University of Zurich, Zurich, Switzerland.
Physiol Rep ; 6(7): e13667, 2018 04.
Article em En | MEDLINE | ID: mdl-29611340
ABSTRACT
Kidney proximal tubules (PTs) contain a high density of mitochondria, which are required to generate ATP to power solute transport. Mitochondrial dysfunction is implicated in the pathogenesis of numerous kidney diseases. Damaged mitochondria are thought to produce excess reactive oxygen species (ROS), which can lead to oxidative stress and activation of cell death pathways. MitoQ is a mitochondrial targeted anti-oxidant that has shown promise in preclinical models of renal diseases. However, recent studies in nonkidney cells have suggested that MitoQ might also have adverse effects. Here, using a live imaging approach, and both in vitro and ex vivo models, we show that MitoQ induces rapid swelling and depolarization of mitochondria in PT cells, but these effects were not observed with SS-31, another targeted anti-oxidant. MitoQ consists of a lipophilic cation (Tetraphenylphosphonium [TPP]) joined to an anti-oxidant component (quinone) by a 10-carbon alkyl chain, which is thought to insert into the inner mitochondrial membrane (IMM). We found that mitochondrial swelling and depolarization was also induced by dodecyltriphenylphosphomium (DTPP), which consists of TPP and the alkyl chain, but not by TPP alone. Surprisingly, MitoQ-induced mitochondrial swelling occurred in the absence of a decrease in oxygen consumption rate. We also found that DTPP directly increased the permeability of artificial liposomes with a cardiolipin content similar to that of the IMM. In summary, MitoQ causes mitochondrial swelling and depolarization in PT cells by a mechanism unrelated to anti-oxidant activity, most likely because of increased IMM permeability due to insertion of the alkyl chain.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Organofosforados / Ubiquinona / Túbulos Renais Proximais / Dilatação Mitocondrial / Antioxidantes Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Physiol Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Compostos Organofosforados / Ubiquinona / Túbulos Renais Proximais / Dilatação Mitocondrial / Antioxidantes Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Physiol Rep Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Suíça