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FARAFARA Cure FA

The role of mitochondrial labile iron in Friedreich's ataxia skin fibroblasts sensitivity to ultraviolet A

Mitochondrial labile iron (LI) is a big factor in how sensitive skin cells are to ultraviolet A (UVA)-induced oxidative damage, which leads to cell death. Mitochondria iron overload is a key feature of FA. This group shows that cultured skin cells from FRDA patients are 4 to 10-fold more sensitive to UVA-induced death than their healthy counterparts. They show that FA cells have higher levels of mitochondrial LI (up to 6-fold on average compared to healthy counterparts) and show higher increase in mitochondrial reactive oxygen species (ROS) generation after UVA irradiation (up to 2-fold on average), consistent with their differential sensitivity to UVA. Pre-treatment of the FA cells with a bespoke mitochondrial iron chelator greatly reduces the UVA-mediated cell death and UVA-induced damage to the mitochondrial membrane. These results reveal a link between FA as a disease of mitochondrial iron overload and sensitivity to UVA of skin fibroblasts. These findings suggest that the high levels of mitochondrial LI in FA cells which contribute to high levels of mitochondrial ROS production after UVA irradiation are likely to play a crucial role in the marked sensitivity of these cells to UVA-induced oxidative damage.

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Jane Larkindale

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