Figure 5.
Deferasirox-induced mitochondrial swelling is driven by osmotic gradients independent of respiratory chain activity. (a) TOM-20 staining of mitochondria in OK cells pre-treated for 10 minutes with the respiratory chain complex III inhibitor antimycin A (2.5 µM), or the ATP synthase inhibitor oligomycin (10 µg/ml), or for 1 minute with the uncoupler FCCP (10 µM). None of these interventions prevented mitochondrial swelling after the subsequent addition of DFX (200 µM, scale = 10 µm). (b) Live confocal imaging of OK cells loaded with MitoTracker Deep Red FM. Treatment with DFX (200 μM) alone caused mitochondrial swelling, as expected. In contrast, mitochondrial swelling was prevented in cells incubated with 10% PEG 400 for 5 minutes prior to DFX exposure, to increase cytosolic osmolarity (scale = 10 μM).