Fluorescence resonance energy transfer reveals a binding site of a photosensitizer for photodynamic therapy |
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Authors: | Morris Rachel L Azizuddin Kashif Lam Minh Berlin Jeffrey Nieminen Anna-Liisa Kenney Malcolm E Samia Anna C S Burda Clemens Oleinick Nancy L |
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Institution: | Department of Radiation Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. |
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Abstract: | Phthalocyanine (Pc) 4, like many photosensitizers for photodynamic therapy (PDT), localizes to intracellular membranes, especially mitochondria. Pc 4-PDT photodamages Bcl-2 and Bcl-xL, antiapoptotic proteins interacting with the permeability transition pore complex that forms at contact sites between the inner and outer mitochondrial membranes. These complexes and the inner membrane are unique in containing the phospholipid cardiolipin. Nonyl-acridine orange (NAO) is a specific probe of cardiolipin. Here we show evidence for fluorescence resonance energy transfer from NAO to Pc 4, defining a binding site for the photosensitizer. This observation establishes an innovative tool for exploring the localization of other photosensitizers and additional fluorescent, mitochondrion-localizing drugs having appropriate spectral properties. |
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