Iron is an important trace element and found in the active centre of many enzymes. It is usually bound intracellularly in a protected and non-redox-active way or safely stored in ferritin. However, during degradation of iron-containing proteins inside lysosomes iron is released and at least temporarily redox-active. If hydrogen peroxide that has escaped the cellular antioxidative defence system diffuses into lysosomes and reacts with iron (Fenton reaction), the highly reactive hydroxyl radical is formed. Depending on the amount of the radical produced, intralysosomal material can either be cross-linked resulting in the production of the non-degradable age pigment lipofuscin, or the lysosomal membrane can be peroxidized and eventually rupture with release of apoptosis-inducing lysosomal enzymes. Since iron is usually not excreted, with time its level increases in post-mitotic cells and it becomes bound to lipofuscin. The accumulation of lipofuscin and the resulting misdirection of lysosomal enzymes in the unfruitful attempt to degrade this age pigment lead to a reduction of degradative capacity of the cell and, therefore, abnormal protein aggregates that occur e.g. in Parkinson's or Alzheimer's disease are not degraded.

Here it is shown that lysosomes contain the major part of redox-active iron and demonstrated that its reactivity can be modulated pharmacologically by iron chelators preserving lysosomal stability and protecting against oxidative stress-induced cell damage. Temporary intralysosomal chelation of iron also occurs naturally by autophagy of iron-binding proteins. The use of iron chelators may offer an opportunity to prevent lipofuscin accumulation.