MnSOD

Manganese superoxide dismutase (MnSOD), also known as SOD2, is a mitochondrial matrix enzyme that protects cells from oxidative damage. It is encoded by the nuclear SOD2 gene and synthesized with a mitochondrial targeting sequence that directs the precursor protein to the mitochondrion, where the targeting peptide is removed to yield the mature enzyme. MnSOD binds a manganese ion at its active site and commonly forms a homotetramer composed of four subunits, each with one Mn atom. The enzyme catalyzes the dismutation of superoxide radicals (O2−) into hydrogen peroxide (H2O2) and molecular oxygen (O2).

Superoxide is generated mainly by the mitochondrial electron transport chain. By rapidly converting O2− to H2O2, MnSOD reduces oxidative damage to mitochondrial DNA, lipids, and proteins, supporting mitochondrial function and cell survival. Hydrogen peroxide can be further detoxified by catalase and glutathione peroxidases. Genetic deletion of MnSOD in mice leads to early embryonic lethality, illustrating its essential role; partial deficiency or dysregulation is associated with increased oxidative stress and has been studied in aging and various diseases, including cancer and neurodegenerative disorders.

Regulation of SOD2 expression occurs at transcriptional and post-translational levels. Transcription factors such as p53, NF-κB, and FOXO family members can influence SOD2 transcription in response to stress. Post-translational modifications, including acetylation and deacetylation by mitochondrial SIRT3, modulate MnSOD activity and mitochondrial localization. Clinically, MnSOD levels or activity are investigated as biomarkers in some conditions, and strategies to modulate MnSOD are explored in research on aging, cancer, and neurodegeneration.