Gene structure for mouse glutathione reductase, including a putative mitochondrial targeting signal

Glutathione reductase (GR) is an important component of cellular antioxidant defense functions. Although GR activities are found in mitochondria and cytoplasm, the sorting mechanisms of mammalian GR into mitochondria have not been elucidated. To identify the mouse GR gene structure, including a sequence for a potential mitochondrial targeting signal (MTS), we screened a mouse genomic library and isolated four contiguous clones that covered the entire coding region of the gene. The coding region is composed of 13 exons. Exon 1 has two in-frame start codons separated by a sequence for an arginine-rich peptide segment. Expression studies, in which Chinese hamster ovary cells were transiently transfected with a plasmid containing the first 78 bp of the mouse exon 1 attached 5' to the human GR cDNA, showed marked and selective increases in mitochondrial GR activities. The data indicate that this 78 bp sequence encodes a potential MTS for GR in mice.