Glutathione reductase, mitochondrial (GSR)

Glutathione reductase, mitochondrial is an essential flavoprotein enzyme encoded by the GSR gene. It catalyzes the reduction of glutathione disulfide (GSSG) into two molecules of reduced glutathione (GSH), using NADPH as an electron donor. This reaction maintains high intracellular levels of GSH—a critical antioxidant that protects cells from reactive oxygen species and supports various metabolic processes including detoxification, protein synthesis, DNA repair, and maintenance of iron-sulfur cluster enzymes. The enzyme functions primarily within mitochondria but also exists in cytosolic forms depending on organismal context. Its proper function is vital for cell survival under aerobic conditions; deficiency leads to impaired respiration rates and increased sensitivity to oxidative stress-related diseases such as cancer and neurodegeneration.

Other names

Glutathione-disulfide reductaseGRGRaseGLURGRD1

Drugs that inhibit or modulate this enzyme typically act by blocking its active site or interfering with NADPH/FAD binding, leading to increased cellular oxidative stress and potential cell death—useful for cancer therapy but also a risk for toxicity.