Reactive Oxygen Species in Cellular Signalling and Oxidative Stress: Molecular Mechanisms and Biological Implications

Abstract Reactive oxygen species (ROS) exhibit a paradoxical nature in biological systems. Historically, regarded as deleterious species, ROS are now well recognised as a crucial component of cellular signalling. The excessive accumulation of ROS leads to oxidative damage of biomolecules. In contrast, at low to moderate levels, ROS function as signalling molecules mediating developmental processes and stress adaptation. Acting as a second messenger, ROS activate downstream signalling cascade comprising receptor kinases and redox‐sensitive transcription factors, thereby modulating gene expression. ROS also operate downstream of other signalling molecules, such as calcium, integrating multiple signalling pathways to elicit specific cellular responses. Understanding the dual role of ROS is essential for elucidating their molecular mechanisms in maintaining cellular homeostasis and guiding future research in the fields of human healthcare and crop management. Key Concepts Reactive oxygen species (ROS) are paradoxical molecules that exert both deleterious and beneficial effects, functioning as a damaging agent at high concentration and as a signalling molecule at controlled levels. The spatiotemporal concentration of ROS species within subcellular compartments determines their biological fate, which is governed by production, scavenging, and diffusion rate across organelles. The innate antioxidant‐based defence system functions through three coordinated lines of defence: the first line of defence prevents the formation of ROS at the source, the second interrupts the chain reaction of free radicals, and the third repairs or eliminates damaged ROS. Disruption of redox homeostasis leads to oxidative damage of lipids, proteins and nucleic acids, causing genetic instability, mutation, membrane disintegration and onset of pathological conditions like cancer, neurodegenerative diseases, aging, Alzheimer in humans, as well as premature senescence, programmed cell death, reduced crop growth and yield. Low‐to‐moderate levels of ROS mediate retrograde signalling in plants and humans through a cascade involving protein kinases and transcription factors, thereby eliciting stress‐responsive gene expression. ROS induces reversible or irreversible post‐translational modifications in protein molecules by oxidising amino acid side chains, resulting in activation or inhibition of enzymes, regulating transcription factors and gene expression. In plants, ROS mediates cell‐to‐cell communication, enabling systemic signalling that primes distally located tissues for impending stress. ROS signalling displays cross‐talk with other signalling molecules like Ca 2+ , Reactive Nitrogen Species (RNS) and phytohormones and can functions either upstream or downstream of these signalling pathways, thereby integrating ROS into a complex cellular signalling network.