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Proceedings Paper

Considerations on the role of cardiolipin in cellular responses to PDT
Author(s): Rachel L. Morris; Kashif Azizuddin; Jeffrey C. Berlin; Clemens Burda; Malcolm E. Kenney; Anna C. S. Samia; Nancy L. Oleinick
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Paper Abstract

Cardiolipin is a unique phospholipid containing two phosphatidyl glycerol moieties and four fatty acids per molecule. It is found exclusively in the mitochondrial inner membrane and at the contact sites between the inner and outer membranes. The acridine derivative, nonyl-acridine orange (NAO), is a highly specific probe of cardiolipin, with a binding affinity approximately two orders of magnitude greater than that for binding to other anionic phospholipids. We recently reported that when NAO is bound in the mitochondria of human prostate cancer PC-3 cells and activated at 488 nm, NAO could transfer fluorescence resonance energy to the phthalocyanine photosensitizer Pc 4. This observation indicates that one site of Pc 4 binding is very near to NAO and therefore very near to cardiolipin. The average distance between the two fluorophores was calculated to be 7 nm. In the present study, we have extended the observation to the endogenously synthesized photosensitizer, protoporphyrin IX, an intermediate in heme biosynthesis that is used for photodynamic therapy of several types of malignant and non-malignant conditions. Protoporphyrin IX is generated in the mitochondria but is known to bind to other cellular sites as well, especially the endoplasmic reticulum. The ability of this molecule to accept resonance energy from NAO in cells is consistent with a localization of at least some of the molecules in the mitochondria either on the inner membrane, the site of cardiolipin, or within about 10 nm of it. Since protoporphyrin IX binds with high affinity to the peripheral benzodiazepine receptor, a component of the permeability transition pore complex that forms at contact sites between the inner and outer membranes, our observations provide evidence for the close association of several critical molecules for mitochondrial functions and suggest that cardiolipin may be an early oxidative target during PDT with at least two photosensitizers.

Paper Details

Date Published: 14 June 2004
PDF: 9 pages
Proc. SPIE 5315, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIII, (14 June 2004); doi: 10.1117/12.531208
Show Author Affiliations
Rachel L. Morris, Case Western Reserve Univ. (United States)
Kashif Azizuddin, Case Western Reserve Univ. (United States)
Jeffrey C. Berlin, Case Western Reserve Univ. (United States)
Clemens Burda, Case Western Reserve Univ. (United States)
Malcolm E. Kenney, Case Western Reserve Univ. (United States)
Anna C. S. Samia, Case Western Reserve Univ. (United States)
Nancy L. Oleinick, Case Western Reserve Univ. (United States)


Published in SPIE Proceedings Vol. 5315:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIII
David Kessel, Editor(s)

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