Redox regulation in Aging: role of protein aggregates

Reactive oxygen species (ROS) are formed continuously in the organism even under physiological conditions. Proteins are prominent targets of oxidation reactions. Such oxidized proteins are either degraded or form protein aggregates. Such protein aggregates are accumulating during cellular aging and influence the metabolism in an aged cell. One of the potential adverse reactions of protein aggregates in aged cells is the aggregate-dependent formation of reactive oxygen species. Protein aggregates are able to incorporate metals, especially iron, which is redox active and can only be partially accessed by chelators. We were able to show that such protein aggregates are contributing substantially to the changes in the pro-oxidative status of aged cells. A special role in this formation of protein aggregate-dependent, metal-induced oxidative stress is played by iron containing proteins, which may be included into the protein aggregates. We could show a contribution of both, cytosolic/ferritin and mitochondrial iron sources. While research is often focusing on the pro-oxidant role of mitochondria in aged cells, other sources – as protein aggregates – of oxidants have to be taken into account.