Glutathione and γ-glutamylcysteine in the antioxidant and survival functions of mitochondria

Mitochondria are both the main producers and targets of ROS (reactive oxygen species). Among the battery of antioxidants that protect mitochondria from ROS, GSH is thought to be essential for the organelle antioxidant function. However, mitochondria cannot synthesize GSH de novo, thus depending on an efficient transport from the cytosol to maintain their redox status. In the present article, we review recent data suggesting that the cellular redox control might not be the main function of GSH, and that its immediate precursor, γGC (γ-glutamylcysteine), can take over the antioxidant role of GSH and protect the mitochondria from excess ROS. Together, GSH and γGC may thus represent an as yet unrecognized defence system relevant for degenerative processes associated with the imbalance in the cellular redox control.