Redox systems of the cell: Possible links and implications

Oxidation-reduction status (redox) is an important regulator of various metabolic functions of the cell. Perturbations in the redox status of cells by external or internal stimuli elicit distinct responses, resulting in alteration of cell function. Glutathione and thioredoxin are two major reducing systems of the eukaryotic cell that maintain redox balance, as well as interact with various transducer and effector molecules to bring about specific responses. However, these two systems differ greatly in their functions and responses to various types of stress. Oxidative stress profoundly impacts them both by direct or indirect oxidation of sulfhydryl groups. Glutathione is a small tripeptide with a single cysteine residue that undergoes oxidation-reduction (1). Thioredoxin (Trx) is an approximately 12-kD protein that contains five cysteine residues (two catalytic and three structural). These cysteines undergo oxidation-reduction reactions in response to oxidants or reductants in the environment (2). To date, the glutathione and thioredoxin systems were considered parallel redox systems.