Oxidative Damage and Antioxidant Defense in Ferroptosis

Abstract

Many new types of regulated cell death have been recently implicated in human health and disease. These regulated cell deaths have different morphological, genetic, biochemical, and functional hallmarks. Ferroptosis was originally described as a carcinogenic RAS-dependent non-apoptotic cell death, and is now defined as a type of regulated necrosis characterized by iron accumulation, lipid peroxidation, and the release of damage-associated molecular patterns (DAMPs). Multiple oxidative and antioxidant systems, acting together autophagy machinery, shape the process of lipid peroxidation during ferroptosis. In particular, the production of reactive oxygen species (ROS) that depends on the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and the mitochondrial respiratory chain promotes lipid peroxidation by lipoxygenase (ALOX) or cytochrome P450 reductase (POR). In contrast, the glutathione (GSH), coenzyme Q10 (CoQ10), and tetrahydrobiopterin (BH 4) system limits oxidative damage during ferroptosis. These antioxidant processes are further transcriptionally regulated by nuclear factor, erythroid 2-like 2 (NFE2L2/NRF2), whereas membrane repair during ferroptotic damage requires the activation of endosomal sorting complexes required for transport (ESCRT)-III. A further understanding of the process and function of ferroptosis may provide precise treatment strategies for disease.

Iron Overload Is Associated With Accelerated Progression of Osteoarthritis: The Role of DMT1 Mediated Iron Homeostasis

“…Our results indicated that iron overload played detrimental effects in OA progression, however, how excess iron damages chondrocytes under OA pathogenic conditions remains unknown. Excess free iron could act as a catalyst to produce large amount of ROS and lead to accumulation of lipid peroxides and ferroptosis (Kuang et al, 2020). Ferroptosis is a newly identified iron dependent cell death and we speculate that ferroptosis is involved in iron overload induced chondrocytes apoptosis.…”

SnO2-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway

“… 56 GSH scavenge ROS and free radicals to protect cells from oxidative damage. 57 Main antioxidant enzymes are GPx, SOD, and CAT. GPx is mainly responsible for removal of hydroperoxides, hence, it may protect membranes, lipids, and proteins from oxidation.…”

Iron Metabolism in Ferroptosis

“…Excess of free reactive iron can cause various types of cell death, including a recently recognized type, ferroptosis. Although the core molecular effector of ferroptosis is unclear, ferroptosis is induced by the activation of iron-dependent lipid peroxidation ( Kuang et al, 2020 ). Significant progress has been made in dissecting the mechanisms that lead to lipid peroxidation and how antioxidant systems or stress proteins regulate ferroptosis.…”