glutaredoxin-2, mitochondrial (GLRX2, GRX2, CGI-133)

Function

• glutathione-dependent oxidoreductase
• facilitates maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress
• role in response to hydrogen peroxide & regulation of apoptosis caused by oxidative stress
• very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides
• can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol & dithiol reactions
• efficiently catalyzes both glutathionylation & deglutathionylation of mitochondrial complex 1, which in turn regulates the superoxide production by the complex
• overexpression decreases the susceptibility to apoptosis & prevents loss of cardiolipin & cytochrome c release
• 2Fe-2S present in the homodimer
  • leads to inactivation of the enzyme
  • may serve as a redox sensor:
    • presence of one-electron oxidants or reductants lead to loss of the 2Fe-2S cluster, subsequent monomerization & activation of the enzyme
• unlike other glutaredoxins, not inhibited by oxidation of structural Cys residues

Kinetic parameters:

• KM=5.9 mM for GSH
• KM=0.77 mM for glutathionylated ribonuclease A

Structure

• monomer, active form
• homodimer, inactive form,
  • homodimer is probably linked by 1 2Fe-2S cluster
• - belongs to the glutaredoxin family

Compartment

• isoform 1: mitochondrion
• isoform 2: nucleus

Alternative splicing

named isoforms=2

Expression

• widely expressed
• expressed in brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung
• not expressed in peripheral blood leukocytes

Pathology

• absence of GLRX2 sensitizes cells to cell death induced by doxorubicin/adriamycin & phenylarsine oxide

More general terms

• oxidoreductase
• mitochondrial protein

Database

• OMIM: https://mirror.omim.org/entry/606820
• UniProt: http://www.uniprot.org/uniprot/Q9NS18.html