Role of lipid hydroperoxides in photo-oxidative stress signaling

Photosensitized peroxidation of membrane lipids has been implicated in skin pathologies such as phototoxicity, premature aging, and carcinogenesis, and may play a role in the antitumor effects of photodynamic therapy. Lipid hydroperoxides (LOOHs) are prominent early products of photoperoxidation that typically arise via singlet oxygen ((1)O(2)) attack. Nascent LOOHs can have several possible fates, including (i) iron-catalyzed one-electron reduction to chain-initiating free radicals, which exacerbate peroxidative damage, (ii) selenoperoxidase-catalyzed two-electron reduction to relatively innocuous alcohols, and (iii) translocation to other membranes, where reactions noted in (i) or (ii) might take place. In addition, LOOHs, like other stress-associated lipid metabolites/peroxidation products (e.g., arachidonate, diacylglycerol, ceramide, 4-hydroxynonenal), may act as signaling molecules. Intermembrane transfer of LOOHs may greatly expand their signaling range. When photogenerated rapidly and site-specifically, e.g., in mitochondria, LOOHs may act as early mediators of apoptotic cell death. This review will focus on these various aspects, with special attention to the role of LOOHs in photooxidative signaling.