The redox language in neurodegenerative diseases: oxidative post-translational modifications by hydrogen peroxide

摘要

A In the ER, the major source of ER-ROS production is from the process of oxidative protein folding for disulfide bond formation. This process is governed by the enzyme ER oxidoreductin 1 (ERO1). NADPH oxidase 4 (NOX4) is also involved in the production of ER-ROS, mainly ER-H2O2. B In the peroxisomes, the major producer of peroxisomal ROS is the process of beta-oxidation of fatty acids. The main player involved is the enzyme, Acyl-CoA oxidase (ACOX). Numerous other enzymes in the peroxisomes also contribute to the production of peroxisomal ROS: xanthine oxidase (XO); d-amino-acid oxidase (DAO); d-aspartate oxidase (DDO); l-pipecolic acid oxidase (PIPOX); l-α-hydroxyacid oxidase (HAO); polyamine oxidase (PAOX). C The main producers of mitochondrial ROS in the mitochondria are from the activity of the electron transport chain (ETC) during oxidative phosphorylation (OXPHOS). The mitochondrial superoxide (O2•−) produced by the ETC is immediately converted to mitochondrial hydrogen peroxide (H2O2) by superoxide dismutase 1 and 2 (SOD1 and SOD2). In general, cellular H2O2 is one of the major and common forms of cellular ROS. Its role as a secondary messenger and its production in these three organelles has raised a suggestion of a potential redox signaling complex among them, highlighting the importance of cellular H2O2 in cellular redox communications. Created with BioRender.com.