GLRX3

Last update 08 May 2025

Basic Info

Synonyms

bA500G10.4, GLRX3, GLRX4

+ [10]

Introduction

Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (By similarity). Required for hemoglobin maturation (PubMed:23615448). Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity.

100 Clinical Results associated with GLRX3

100 Translational Medicine associated with GLRX3

0 Patents (Medical) associated with GLRX3

200

Literatures (Medical) associated with GLRX3

01 Jul 2025·Free Radical Biology and Medicine

The glutathione system maintains the thiol redox balance in the mitochondria of fission yeast

Article

Author: de Cubas, Laura ; Gómez-Armengol, Ferran ; Boronat, Susanna ; Lyublinskaya, Olga ; Ayté, José ; Artemov, Alexey ; Domènech, Alba ; Vega, Montserrat ; Hidalgo, Elena

The thioredoxin and glutathione (GSH)-glutaredoxin electron donor pathways provide a reducing environment to the cell and maintain homeostasis of numerous redox reactions. The abundant tripeptide GSH has multiple roles, including redox buffering, detoxification, peroxide scavenging and iron-sulfur cluster assembly. Glutathione reductase, Pgr1 in fission yeast, maintains glutathione reduced, and it is essential in most organisms. Cells lacking Pgr1 exhibit severe pleiotropic defects. We used multiple approaches to unravel the compartment-specific roles of Pgr1. Our findings confirmed that Pgr1 had dual cytosolic and mitochondrial localization. Mitochondrial homeostasis was severely impaired in Δpgr1 cells and most of these defects were restored by expression of an exclusively mitochondrial Pgr1 isoform. As expected, the cytosol of Δpgr1 cells showed low ratio of reduced-to-oxidized glutathione. However, this did not significantly affect peroxiredoxin-dependent hydrogen peroxide scavenging, suggesting a minimal role, if any, of GSH in cytosolic thiol reduction. The transcriptome of Δpgr1 cells revealed signatures of oxidative stress and iron deprivation, suggesting that the GSH-containing sensor of iron starvation, the glutaredoxin Grx4, is also a sensor of GSH oxidation. In the mitochondria, Pgr1 not only provided the GSH electron donor for the glutaredoxin-based pathway but also recycled mitochondrial Trx2, thereby contributing to thiol redox homeostasis in the matrix. In conclusion, glutathione reductase is essential for maintaining a balanced redox environment in the mitochondria by recycling Trx2, Grx2 and the GSH-containing Grx5, and therefore contributes to the processes of iron-sulfur cluster assembly and respiration, while controlling Grx4 dynamics in the cytosol.

01 Mar 2025·Neurological Sciences

Hypoxia-inducible factor-1 as targets for neuroprotection : from ferroptosis to Parkinson’s disease

Review

Author: Ou, Chaoyan ; Wang, Changyong ; Lv, Shanyu ; Zhao, Hongyan ; Chen, Kemiao ; He, Yonghua ; He, Guoguo ; Qu, Minghai ; Liang, Hongshuo

BACKGROUNDParkinson's disease (PD) is a neurodegenerative disease characterized by motor paralysis, tremor,and cognitive impairment. Risk factors such as brain hypoxia caused by aging and abnormal expression of HIF-1α areconsidered to be key to the development of PD, including α-synuclein accumulation and ferroptosis. However, therelationship between HIF-1α signaling and ferroptosis in PD has not been elucidated. The stable expression of HIF-1αinhibits the pathological development of PD. Aging aggravates PD pathology by promoting α-synuclein accumulationand oxidative stress.METHODSThe literature on lipid peroxidation, oxidative stress, iron metabolism and other key factors in Parkinson'sdisease in recent years was reviewed through a variety of literature search channels, such as PubMed and Elsevier.RESULTSHIF-1α mediated ferroptosis through oxidative stress and GPX4-GSH system. HIF-1α mediates ferroptosisthrough Keap1-Nrf2-ARE, Grx3 and Grx4. HIF-1α mediates ferroptosis through iron metabolism.CONCLUSIONThis article reviews the oxygen-dependent regulatory mechanism of HIF-1α and its role in cerebralhypoxia homeostasis. Studies in the past decade have shown that Hif-1α mediated ferroptosis is important in PD.HIF-1α has a dual role, depending on the degree of cellular hypoxia and the environment. The equilibrium complexityneeds to be explained, and the role of ferroptosis needs to be investigated. The literature shows that the stabilizationof HIF-1α with PHD inhibitors and the combination of antioxidants and iron chelators are potential therapeuticdirections. In the future, the optimal use time and dose of inhibitors should be studied to improve the efficacy.

01 Feb 2025·Archives of Biochemistry and Biophysics

Schizosaccharomyces pombe Grx4 is subject to autophagic degradation under nitrogen- and iron- starvation and ER-stress

Article

Author: Li, Rong ; Huang, Ying

Glutaredoxins (Grxs) are small, heat-stable proteins that serve as multi-functional glutathione （GSH）-dependent thiol transferases. Recent studies have elucidated their role in regulating cellular iron and copper homeostases. In Schizosaccharomyces pombe, five Grxs (Grx1-5) have been identified. Among them， Grx4 and its homologs possess a C-terminal glutaredoxin domain (GRX) and an N-terminal thioredoxin-like domain (TRX). The functional roles of the GRX and TRX domains in Grx4 were investigated by constructing strains that express a truncated Grx4 under the regulation of either a constitutive cam1 promoter or its native promoter. Our findings indicated that two autophagy-related (Atg) protein 8 (Atg8)-interacting motifs (AIM), FLKI and FQEI, in the TRX domain of Grx4 are sufficient to induce autophagic degradation under nitrogen- and iron-starvation, respectively. Moreover, the expression level of a vacuolar ferrous iron transporter Pcl1 was altered in Δatg5 or Δatg8 strains under iron starvation,suggesting that autophagy is required for maintaining iron homeostasis in S. pombe. Further investigations revealed that Grx4 is required for cellular survival and endoplasmic reticulum (ER) autophagy (ER-phagy) during dithiothreitol (DTT) treatment, implying a potential correlation between Grxs and ER-stress. Additionally, loss of Grx4 disrupts nuclear integrity during ER stress, highlighting the versatility and importance of further investigations into the functions of Grx4.

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GLRX3

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