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Blocking mitochondrial permeability transition prevents p53 mitochondrial translocation during skin tumor promotion.

Liu J, St Clair DK, Gu X, Zhao Y

Department of Pharmacology, Toxicology and Neuroscience, LSU Health Sciences Center, Shreveport, LA 71130, USA.

The tumor suppressor p53 can translocate into mitochondria and activate apoptosis. Here we studied whether p53 mitochondrial translocation and subsequent apoptosis were affected by blocking mitochondrial permeability transition pore using cyclosporine A (CsA) and bongkrekic acid (BA) in skin epidermal JB6 cells and skin tissues. Our results demonstrated that CsA and BA blocked TPA-induced p53 translocation, leading to protection against the loss of mitochondrial membrane potential and Complex I activity, and eventually suppression of apoptosis. Thus, our results suggest that mitochondrial permeability transition is required for p53 mitochondrial translocation.

Published 8 April 2008 in FEBS Lett, 582(9): 1319-24.
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