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Glutathione, glutaredoxins, and iron.

ABSTRACT

Glutathione is the most abundant cellular low molecular weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of glutathione and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent advances: The function of glutathione as redox buffer or antioxidant is increasingly being questioned. New functions, especially functions connected to the cellular iron homeostasis were elucidated. Via the formation of iron complexes, glutathione is an important player in all aspects of iron metabolism: sensing and regulation of iron levels, iron trafficking, and biosynthesis of iron cofactors. The variety of glutathione coordinated iron complexes and their functions with a special focus on FeS-glutaredoxins are summarized in this review. Interestingly, glutathione analogues that function as major low molecular weight thiols in organisms lacking glutathione resemble the functions in iron homeostasis.Since these iron-related functions are most likely also connected to thiol redox chemistry, it is difficult to distinguish between mechanisms related to either redox or iron metabolisms.The ability of glutathione to coordinate iron in different complexes with or without proteins needs further investigation. The discovery of new Fe-glutathione complexes and their physiological functions will significantly advance our understanding of cellular iron homeostasis.