THE ROLE OF LABILE IRON IN SOLAR UVA RADIATION-INDUCED MITOCHONDRIAL DAMAGE – NOVEL MITOCHONDRIAL SENSORS AND IRON CHELATORS FOR PHOTOPROTECTION

Abstract

Iron plays a crucial role in a number of vital cellular processes including division and respiration. However under exposure to environmental stress or in some neurological pathologies, iron as labile iron pool (LIP) is a threat to cell integrity by acting as catalyst of oxidative damage to biomolecules [1, 2]. Mitochondria are a major destination for LIP, making these organelles particularly susceptible to oxidative damage notably following exposure to solar ultraviolet A (UVA, 320-400 nm). Upon exposure of cells to UVA, the incurred labile iron-mediated damage to mitochondria leads to cell death. This suggests that targeted removal of mitochondrial labile iron from these organelles using highly specific tools may be an effective strategy to protect skin cells against the harmful effects of UVA. We first developed two distinct generations of mitochondria-homing “SS-peptides” which proved valuable tools to deliver to cells bidentate iron chelators capable of sensitively evaluating the changes in LIP [3, 4]. Subsequently we designed novel mitochondria-targeted hexadentate iron chelators with higher affinity for iron compared to bidentate iron sensors [5]. The photoprotective capabilities of this novel generation of compounds against UVA-induced oxidative damage and cell death will be described, using cultured primary skin fibroblasts as a cell model.