Journal
REDOX BIOLOGY
Volume 43, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2021.101975
Keywords
Glutaredoxin; Redox regulation; Glutathionylation; Deglutathionylation; Iron homeostasis; Grxs phylogenetics
Categories
Funding
- Swedish Cancer Society [961]
- Swedish Research Council Medicine [13X-3529]
- Swedish Fulbright Commission
- Fundacao para a Ciencia e Tecnologia, Portugal (FCT) [UIDP/04138/2020, UIDB/04138/2020]
- Fundacao para a Ciencia e Tecnologia through Norma Transitoria [DL57/2016/CP1376/CT002]
- Fundacao para a Ciencia e Tecnologia through Assistant Researcher grant [CEECIND/03023/2017]
- iMed
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Glutaredoxin (Grx) is a small protein with an active site cysteine pair that regulates redox reactions through glutathionylation, playing a crucial role in various physiological and pathological conditions.
Glutaredoxin, Grx, is a small protein containing an active site cysteine pair and was discovered in 1976 by Arne Holmgren. The Grx system, comprised of Grx, glutathione, glutathione reductase, and NADPH, was first described as an electron donor for Ribonucleotide Reductase but, from the first discovery in E.coli, the Grx family has impressively grown, particularly in the last two decades. Several isoforms have been described in different organisms (from bacteria to humans) and with different functions. The unique characteristic of Grxs is their ability to catalyse glutathione-dependent redox regulation via glutathionylation, the conjugation of glutathione to a substrate, and its reverse reaction, deglutathionylation. Grxs have also recently been enrolled in iron sulphur cluster formation. These functions have been implied in various physiological and pathological conditions, from immune defense to neurodegeneration and cancer development thus making Grx a possible drug target. This review aims to give an overview on Grxs, starting by a phylogenetic analysis of vertebrate Grxs, followed by an analysis of the mechanisms of action, the specific characteristics of the different human isoforms and a discussion on aspects related to human physiology and diseases.
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