Glutathione reductase, mitochondrial

Function

Catalyzes the reduction of glutathione disulfide (GSSG) to reduced glutathione (GSH). Constitutes the major mechanism to maintain a high GSH:GSSG ratio in the cytosol.

Classification

Family (Pfam)

PF07992 Pyr_redox_2, PF02852 Pyr_redox_dim

InterPro

FAD/NAD-bd_sf, FAD/NAD-binding_dom, FAD/NAD-linked_Rdtase_dimer_sf, Glutathione_Rdtase_euk/bac, GSHR/TRXR-like, Pyr_nuc-diS_OxRdtase, Pyr_nucl-diS_OxRdtase_dimer, Pyr_OxRdtase_I_AS

Functional cluster

Oxidoreductases & Polyketide Synthases

Experimental structures · PDB · 27

• 1ALG NMR
• 1BWC X-ray 2.10A
• 1DNC X-ray 1.70A
• 1GRA X-ray 2.00A
• 1GRB X-ray 1.85A
• 1GRE X-ray 2.00A
• 1GRF X-ray 2.00A
• 1GRG X-ray 2.00A
• 1GRH X-ray 3.00A
• 1GRT X-ray 2.30A
• 1GSN X-ray 1.70A
• 1K4Q X-ray 1.90A
• … and 15 more

A predicted model is available from AlphaFold.

Gene Ontology · 12

• GO:0005829 cytosol
• GO:0009897 external side of plasma membrane
• GO:0070062 extracellular exosome
• GO:0005759 mitochondrial matrix
• GO:0005739 mitochondrion
• GO:0009055 electron transfer activity
• GO:0050660 flavin adenine dinucleotide binding
• GO:0004362 glutathione-disulfide reductase (NADPH) activity
• GO:0050661 NADP binding
• GO:0045454 cell redox homeostasis
• GO:0034599 cellular response to oxidative stress
• GO:0006749 glutathione metabolic process

Disease associations

• hemolytic anemia due to glutathione reductase deficiency MONDO:0019531

Drugs targeting this protein · 2

• OXIGLUTATIONE other
• CARMUSTINE inhibitor

Related proteins · sequence + function similarity

• Glutathione reductase, mitochondrial 0.97
• Glutathione reductase, mitochondrial 0.96
• Thioredoxin reductase 2, mitochondrial 0.86
• Thioredoxin reductase 2, mitochondrial 0.86
• Thioredoxin reductase 2, mitochondrial 0.85
• Glutathione reductase 0.85
• Thioredoxin reductase 3 0.84
• Thioredoxin reductase 2, mitochondrial 0.84
• Glutathione reductase 0.83
• Thioredoxin reductase 3 0.83
• Thioredoxin reductase 2, mitochondrial 0.81
• Glutathione reductase, mitochondrial 0.80

Co-cited proteins · studied together in the literature

• Glutathione reductase, mitochondrial 1 shared papers

Literature · 21 cited papers

• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Expression of glutathione reductase splice variants in human tissues. Biochem. Genet. · 2010
• Catalytic cycle of human glutathione reductase near 1 A resolution. J. Mol. Biol. · 2008
• Molecular basis of glutathione reductase deficiency in human blood cells. Blood · 2007
• A fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme. J. Am. Chem. Soc. · 2006
• DNA sequence and analysis of human chromosome 8. Nature · 2006
• Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Structural organization of the human glutathione reductase (GSR) gene: determination of correct cDNA sequence and identification of a mitochondrial leader sequence. Biochem. Biophys. Res. Commun. · 2000
• … and 9 more in the literature graph