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The targeted antioxidant MitoQ causes mitochondrial swelling and depolarization in kidney tissue

Author：Esther M. Gottwald, Michael Duss, Milica Bugarski, Dominik Haenni, Claus D. Schuh, Ehud M. Landau, Andrew M. Hall   《Physiological Reports》

ABSTRACTS
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 antioxidant 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 SS31, another targeted antioxidant. MitoQ consists of a lipophilic cation (Tetraphenylphosphonium [TPP]) joined to an antioxidant component (quinone) by a 10carbon 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, MitoQinduced 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 antioxidant activity, most likely because of increased IMM permeability due to insertion of the alkyl chain.
SCREENSHOT

RELATED PRODUCTS
 SS31
CHAINING
https://physoc.onlinelibrary.wiley.com/doi/abs/10.14814/phy2.13667
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