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Abbreviations : 1 O 2 singlet oxygen, 4-HNE 4-hydroxynonenal, AKT protein kinase B, ARE antioxidant response element, ATF6 activating transcription factor 6, ATM ataxia telangiectasia mutated, ATP adenosine triphosphate, α-MSH alpha-melanocyte-stimulating hormone, α-syn alpha-synuclein, BIBR1532 telomerase inhibitor BIBR1532, CAP cold atmospheric plasma, CAT catalase, CD8 + T cell CD8-positive T lymphocyte, cGAS cyclic GMP–AMP synthase, CFU colony-forming unit, CHOP C/EBP homologous protein, C/EBPα CCAAT/enhancer-binding protein alpha, CSC cancer stem cell, Cys118 cysteine residue at position 118, DAMPs damage-associated molecular patterns, DHP dry hydrogen peroxide, DNA deoxyribonucleic acid, Duox1 dual oxidase 1, EAAT1 excitatory amino acid transporter 1, EAAT3 excitatory amino acid transporter 3, ECM extracellular matrix, ecto-CRT ectopic calreticulin exposure, EGF epidermal growth factor, EGFR epidermal growth factor receptor, eIF2α eukaryotic initiation factor 2 alpha, EMT epithelial–mesenchymal transition, ER endoplasmic reticulum, ERCC1 excision repair cross-complementation group 1, ERK extracellular signal-regulated kinase, eWAT epididymal white adipose tissue, FLASH ultra-high dose rate radiotherapy, FLP-1 FMRFamide-like neuropeptide-1, FOXO1 forkhead box O1, FOXO3a forkhead box O3a, FSP1 ferroptosis suppressor protein 1, FTO fat mass and obesity-associated protein, GPX4 glutathione peroxidase 4, GSK3β glycogen synthase kinase 3 beta, H 2 O 2 hydrogen peroxide, HIF-1α hypoxia-inducible factor-1 alpha, HIIT high-intensity interval training, HMGB1 high-mobility group box 1, HO-1 heme oxygenase-1, HOCl hypochlorous acid, ICD immunogenic cell death, ingWAT inguinal white adipose tissue, IRE1 inositol-requiring enzyme 1, JNK c-Jun N-terminal kinase, Keap1 Kelch-like ECH-associated protein 1, Ki-67 marker of cellular proliferation, LGR5 + leucine-rich repeat-containing G-protein-coupled receptor 5-positive, LOO• lipid peroxyl radical, LOOH lipid hydroperoxide, LOOH• lipid hydroperoxyl radical, LPA lysophosphatidic acid, MAPK mitogen-activated protein kinase, MDA malondialdehyde, MnSOD manganese superoxide dismutase, MMP-8 matrix metalloproteinase-8, MMP-13 matrix metalloproteinase-13, mTOR mechanistic target of rapamycin, mTORC2 mechanistic target of rapamycin complex 2, MyoD myogenic differentiation 1, NADPH nicotinamide adenine dinucleotide phosphate, NF-κB nuclear factor-Κb, NO₂⁻ nitrite, NOX2 NADPH oxidase 2, NPR-4 neuropeptide receptor 4, NQO1 NAD(P)H quinone dehydrogenase 1, NRF2 nuclear factor erythroid 2–related factor 2, NSCLC non-small-cell lung cancer, nAChRα7 nicotinic acetylcholine receptor alpha-7 subunit, O 2 molecular oxygen, •O 2 − superoxide anion, O₃ ozone, PAM plasma-activated medium, PD Parkinson’s disease, PD-1 programmed cell death protein-1, PERK protein kinase RNA-like endoplasmic reticulum kinase, PI3K phosphoinositide 3-kinase, PKC-1 protein kinase C-1, PLCγ phospholipase C gamma, PPARγ peroxisome proliferator-activated receptor gamma, p38 p38 mitogen-activated protein kinase, p66Shc 66 kDa Src homology and collagen adaptor protein, PTGS2 prostaglandin-endoperoxide synthase 2, RAD51 RAD51 recombinase, RAS rat sarcoma proto-oncogene, Rictor rapamycin-insensitive companion of mTOR, RLU relative light unit, RNS reactive nitrogen species, RONS reactive oxygen and nitrogen species, ROS reactive oxygen species, RSL3 RAS-selective lethal 3, SCC squamous cell carcinoma, SI A H 2 (SIAH2) seven in absentia homolog 2, SKN-1 skinhead-1 (Caenorhabditis elegans NRF2 ortholog), SOD superoxide dismutase, SOD2 superoxide dismutase 2, SOD3 superoxide dismutase 3, Spd spermidine, STING stimulator of interferon genes, TAC transverse aortic constriction, TNBC triple-negative breast cancer, TRIM25 tripartite motif-containing protein 25, TrxR1 thioredoxin reductase 1, Tubastatin A selective histone deacetylase 6 inhibitor, UPR unfolded protein response, UV ultraviolet radiation, UVB ultraviolet B radiation, XBP1 X-box binding protein 1, •OH hydroxyl radical Radical ROS in disease pathogenesis Mechanisms of pathogenic signaling Radical ROS drive disease pathogenesis by acting as highly reactive, short-range cytotoxic agents, primarily through two interconnected mechanisms, i.e., direct genomic damage and the initiation of self-amplifying lipid peroxidation cascades (Fig