Intermembrane Translocation of Photodynamically Generated Lipid Hydroperoxides: Broadcasting of Redox Damage

Lipid hydroperoxides (LOOHs), including cholesterol‐ and phospholipid‐derived species, are reactive intermediates that arise during photosensitized peroxidation of unsaturated lipids in biological membranes. These intermediates may appear in cancer cell membranes during anti‐tumor photodynamic therapy (PDT). Photodynamically generated LOOHs have several different fates, including (a) iron‐catalyzed one‐electron reduction to free radical species which trigger damaging chain peroxidation reactions, (b) selenoperoxidase‐catalyzed two‐electron reduction to redox‐inert alcohols (LOHs), and (c) spontaneous or protein‐mediated translocation to other lipid membrane compartments where (a) or (b) may take place. These different LOOH fates will be described in this review, but with special attention to category (c), which the authors were the first to describe and characterize. Seminal early findings on cholesterol hydroperoxide (ChOOH) translocation and its potential negative consequences will be discussed. In reviewing this work, we wish to congratulate Jean Cadet, for his many outstanding accomplishments as a photobiologist and P&P editor. Membrane‐bound photosensitizers can generate lipid hydroperoxides such as cholesterol‐derived species (ChOOHs). Cholesterol‐rich plasma membranes of mammalian cells could give high yields of these ChOOHs. In the presence of cholesterol trafficking proteins, the ChOOHs can be transported to other membranes such as those in mitochondria, putting the acceptors at risk of ChOOH one‐electron turnover with ensuing damage/dysfunction. During exposure of malignant steroidogenic tissues to photodynamic therapy (PDT), ChOOH translocation could be a significant contributor to cancer cell death. These and other aspects of lipid hydroperoxide translocation in photodynamic systems are discussed in this review.