Radiation-induced lysosomal iron reactivity: implications for radioprotective therapy.
A novel mechanism of radiosensitization involves radiation-enhanced autophagy of damaged mitochondria and various metalloproteins, by which iron accumulates within lysosomes. Hydrogen peroxide, formed by the radiolytic cleavage of water, generates in the presence of lysosomal redox-active iron extremely reactive hydroxyl radicals by Fenton-type chemistry. Subsequent peroxidative damage of lysosomal membranes initiates release of harmful content from ruptured lysosomes that triggers a cascade of events eventuating in DNA damage and apoptotic or necrotic cell death. This article reviews the role of lysosomal destabilization in radiation-induced cell damage and death. The potential effects of iron chelation therapy targeted to the lysosomes for protection of normal tissues against unwanted effects by radiation is also discussed.
Persson
H Lennart
HL
Division of Pulmonary Medicine, Faculty of Health Sciences, University of Linköping, Linköping, Sweden. lenpe@inr.liu.se
D007501:Iron / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress / Q000502:physiology*; D011837:Radiation-Protective Agents / Q000378:metabolism*
D011837:Radiation-Protective Agents; D007501:Iron