RESPONSE TO ANTIOXIDANT THERAPY: IMPACT OF THE NITROSO-REDOX BALANCE IN RESTORING PROTEASES AND MITOCHONDRIAL FUNCTION IN A PROGEROID DISEASE

Abstract

Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) do not just generate molecular stress but are also signalling molecules with regulatory functions. The nitroso-redox balance, which is the balance between ROS and RNS, plays a role in many intracellular functions including metabolism and mitochondrial activity. Antioxidant therapy is increasingly proposed to treat diseases associated with oxidative stress. However, nowadays, side effects of antioxidant treatments force to reconsider the beneficial therapeutic interest of this approach. Here, we show that antioxidant treatment poorly reverts cellular and mitochondrial defects from a human progeroid disease associated with altered nitroso-redox imbalance. Conversely, full reversion of the cellular and mitochondrial defects is achieved by reducing both ROS and RNS levels. Intriguingly, establishment of an appropriate nitroso-redox balance seems to play a major role in the correction of defects in progeroid cells than simply reducing the levels of these molecules. We will discuss the impact of such treatments on overexpression of proteases and impaired mitochondrial function and the opportunity to reconsider the use of different class of antioxidant molecules in the context of a progeroid dysfunction.