Manganese superoxide dismutase (SOD2) (MnSOD)

Manganese superoxide dismutase (MnSOD), also known as SOD2, is a vital antioxidant enzyme located in the mitochondrial matrix that serves as the primary defense against superoxide radicals generated during oxidative phosphorylation [1, 2]. It catalyzes the conversion of superoxide radicals into oxygen and hydrogen peroxide, thereby preventing the formation of highly reactive hydroxyl radicals and peroxynitrite, which can damage mitochondrial DNA, proteins, and lipids [1, 3]. MnSOD plays a complex role in disease; it is often downregulated in early-stage cancers, acting as a tumor suppressor, but can be upregulated in advanced stages to promote tumor cell survival and metastasis [4]. In therapeutic contexts, MnSOD is targeted using small-molecule SOD mimics like Avasopasem manganese, which are designed to replicate the enzyme's catalytic activity to protect healthy tissues from radiation-induced damage and treat inflammatory conditions [5]. These drugs function by cycling the oxidation state of a coordinated metal ion (usually manganese) to neutralize superoxide, effectively bypassing or supplementing endogenous MnSOD activity [3, 5]. (Citations: [1] UniProt P04179; [2] NCBI Gene ID 6648; [3] PubChem CID 16212409; [4] Galasso et al., Int J Mol Sci 2020; [5] Maples et al., Expert Opin Investig Drugs 2021).

Other names

SOD2Superoxide dismutase [Mn], mitochondrialManganese-dependent superoxide dismutaseMNSODIndophenoloxidase BIPOB

Catalytic dismutation of superoxide radicals into molecular oxygen and hydrogen peroxide through a cyclic reduction and oxidation of the manganese metal center.