Identification, Expression Pattern, and Characterization of

CHRISTOPH HUDEMANN, MARIA ELISABET LÖNN, JOSÉ RODRIGO GODOY, FARNAZ ZAHEDI AVVAL,FRANCISCO CAPANI,3 ARNE HOLMGREN,1AND CHRISTOPHER HORST LILLIG1,2

ANTIOXIDANTS & REDOX SIGNALING

MARY ANN LIEBERT INC

Año: 2009 vol. 11 p. 1 - 13

1523-0864

Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase involved in the maintenance of mitochondrialredox homeostasis. Grx2 was first characterized as mitochondrial protein, but alternative mRNA variantslacking the transit peptide-encoding first exon were demonstrated for human and proposed for mouse. We systematicallyscreened for alternative transcript variants of mouse Grx2. We identified a total of six exons, threeconstitutive (II, III, and IV), two alternative first exons (exons Ia and Ic), and one single-cassette exon (exon IIIb)located between exons III and IV. Exons Ic and IIIb are not present in the human genome; mice lack humanexon Ib. The six exons give rise to five transcript variants that encode three protein isoforms: mitochondrialGrx2a, a cytosolic isoform that is homologous to the cytosolic/nuclear human Grx2c and present in specificcells of many tissues and the testis-specific isoform Grx2d that is unique to mice. Mouse Grx2c can form aniron/sulfur cluster–bridged dimer, is enzymatically active as a monomer, and can donate electrons to ribonucleotidereductase. Testicular cells lack mitochondrial Grx2a but contain cytosolic Grx2. Prominent immunostainingwas detected in spermatogonia and spermatids. These results provide evidence for additional functionsof Grx2 in the cytosol, in cell proliferation, and in cellular differentiation. Antioxid. Redox Signal. 11, 1–14.Antioxid. Redox Signal. 11, 1–14.