A powerful mitochondria-targeted iron chelator affords high photoprotection against solar ultraviolet A radiation

TY - JOUR

T1 - A powerful mitochondria-targeted iron chelator affords high photoprotection against solar ultraviolet A radiation

AU - Reelfs, Olivier Sylvian

AU - Abbate, Vincenzo

AU - Hider, Robert Charles

AU - Pourzand, Charareh

PY - 2016/8

Y1 - 2016/8

N2 - Mitochondria are the principal destination for labile iron (LI), making these organelles particularly susceptible to oxidative damage upon exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The LI-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via ATP depletion. Therefore targeted removal of mitochondrial LI via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria- homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, ATP depletion and the ensuing necrotic cell death in skin fibroblasts and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of UVA component of sunlight.

AB - Mitochondria are the principal destination for labile iron (LI), making these organelles particularly susceptible to oxidative damage upon exposure to ultraviolet A (UVA, 320-400 nm), the oxidizing component of sunlight. The LI-mediated oxidative damage caused by UVA to mitochondria leads to necrotic cell death via ATP depletion. Therefore targeted removal of mitochondrial LI via highly specific tools from these organelles may be an effective approach to protect the skin cells against the harmful effects of UVA. In this work, we designed a mitochondria-targeted hexadentate (tricatechol-based) iron chelator linked to mitochondria- homing SS-like peptides. The photoprotective potential of this compound against UVA-induced oxidative damage and cell death was evaluated in cultured primary skin fibroblasts. Our results show that this compound provides unprecedented protection against UVA-induced mitochondrial damage, ATP depletion and the ensuing necrotic cell death in skin fibroblasts and this effect is fully related to its potent iron-chelating property in the organelle. This mitochondria-targeted iron chelator has therefore promising potential for skin photoprotection against the deleterious effects of UVA component of sunlight.

U2 - 10.1016/j.jid.2016.03.041

DO - 10.1016/j.jid.2016.03.041

M3 - Article

SN - 0022-202X

VL - 136

SP - 1692

EP - 1700

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 8

ER -