GLRX5

Last update 08 May 2025

Basic Info

Synonyms

C14orf87, GLRX5, glutaredoxin 5

+ [4]

Introduction

Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer (PubMed:20364084, PubMed:23615440). Receives 2Fe/2S clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion (PubMed:20364084, PubMed:23615440, PubMed:24334290). Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1 (PubMed:20364084).

100 Clinical Results associated with GLRX5

100 Translational Medicine associated with GLRX5

0 Patents (Medical) associated with GLRX5

157

Literatures (Medical) associated with GLRX5

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.

25 Apr 2025·Zhen ci yan jiu = Acupuncture research

[Mechanisms of acupuncture in inhibition of ferroptosis in intracerebral hemorrhage mice based on RNA m6A methylation sequencing].

Article

Author: Liu, Hao ; DU, Jia ; Lou, Ke-Lang ; Li, Xin-Wei ; Ruan, Chen ; Yu, Xiao-Qing ; Guo, Zhong-Wei ; Feng, Pei-Pei

OBJECTIVESTo observe the effect of acupuncture on N6-methyladenosine (m6A) methylation and ferroptosis in brain tissue of mice with intracerebral hemorrhage (ICH), so as to explore its mechanisms underlying promoting neural function recovery.METHODSFifty-four male C57BL/6J mice were randomly divided into sham operation, model and acupuncture groups, with 18 mice in each group. The ICH model was established by injection of the mouse's auto-blood (10 μL) into the right caudate nucleus. Mice of the acupuncture group received acupuncture at "Baihui" (GV20) for 30 min, twice daily for 7 days. The neurological functions (locomotor and balance deficits) were evaluated according to wire hanging test (0-5 points) and balance walking test (0-5 points) before modeling and after treatment. Histopathological changes in the brain were observed by HE staining. RNA-sequencing and m6A- sequencing were used to analyze the differential m6A modification genes. Immunofluorescence and Western blot were used to detect the expression of glutathione peroxidase 4 (Gpx4) and sirtuin 3 (Sirt3) proteins in brain tissue, respectively.RESULTSHE staining showed that in the brain tissue nucleus was pyknotic, inflammatory cells were infiltrated, neurons were edematous and necrotic in the model group, which were relatively milder in the acupuncture group. The sequencing results showed that 592 differentially expressed genes were screened in the model group vs sham operation group, and 849 differentially expressed genes were screened in the acupuncture group vs model group. Five genes that inhibit ferroptosis were obtained by intersecting with genes that inhibit ferroptosis, namely charged multi vesicular body protein (Chmp) 1a, Chmp6, glutaredoxin (Glrx) 5, Gpx4, and Sirt3. Compared with the sham operation group, the wire hanging test and balance walking test scores, gene expression levels of Chmp1a, Chmp6, Glrx5, Gpx4, and Sirt3, Gpx4/NeuN and Sirt3/NeuN co-expressed fluorescence intensity, the protein expressions of Gpx4 and Sirt3 in brain tissue were all significantly decreased in the model group (P<0.01). Following the interventions, the wire hanging test and balance walking test scores, gene expression levels of Chmp1a, Chmp6, Glrx5, Gpx4, and Sirt3, Gpx4/NeuN and Sirt3/NeuN co-expressed fluorescence intensity, the protein expressions of Gpx4 and Sirt3 in brain tissue were all significantly increased in the acupuncture group compared with the model group (P<0.01, P<0.05).CONCLUSIONSAcupuncture can ameliorate neurological deficits, which may be associated with its function in improving m6A RNA modification and RNA expression in mice with ICH, and promoting the expression of ferroptosis antioxidation related proteins Gpx4 and Sirt3 in brain tissue.

01 Apr 2025·Journal of Biological Chemistry

Mitochondrial glutaredoxin Grx5 functions as a central hub for cellular iron-sulfur cluster assembly

Article

Author: Pain, Debkumar ; Singh, Pratibha ; Dancis, Andrew ; Pandey, Ashutosh K ; Pain, Jayashree

Iron-sulfur (Fe-S) protein biogenesis in eukaryotes is mediated by two different machineries-one in the mitochondria and another in the cytoplasm. Glutaredoxin 5 (Grx5) is a component of the mitochondrial iron-sulfur cluster machinery. Here, we define the roles of Grx5 in maintaining overall mitochondrial/cellular Fe-S protein biogenesis, utilizing mitochondria and cytoplasm isolated from Saccharomyces cerevisiae cells. We previously demonstrated that isolated wild-type (WT) mitochondria themselves can synthesize new Fe-S clusters, but isolated WT cytoplasm alone cannot do so unless it is mixed with WT mitochondria. WT mitochondria generate an intermediate, called (Fe-S)_int, that is exported to the cytoplasm and utilized for cytoplasmic Fe-S cluster assembly. We here show that mitochondria lacking endogenous Grx5 (Grx5↓) failed to synthesize Fe-S clusters for proteins within the organelle. Similarly, Grx5↓ mitochondria were unable to synthesize (Fe-S)_int, as judged by their inability to promote Fe-S cluster biosynthesis in WT cytoplasm. Most importantly, purified Grx5 precursor protein, imported into isolated Grx5↓ mitochondria, rescued these Fe-S cluster synthesis/trafficking defects. Notably, mitochondria lacking immediate downstream components of the mitochondrial iron-sulfur cluster machinery (Isa1 or Isa2) could synthesize [2Fe-2S] but not [4Fe-4S] clusters within the organelle. Isa1↓ (or Isa2↓) mitochondria could still support Fe-S cluster biosynthesis in WT cytoplasm. These results provide evidence for Grx5 serving as a central hub for Fe-S cluster intermediate trafficking within mitochondria and export to the cytoplasm. Grx5 is conserved from yeast to humans, and deficiency or mutation causes fatal human diseases. Data as presented here will be informative for human physiology.

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GLRX5

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