Melatonin as a hub signal integrating redox and hormonal crosstalk with multi-omics regulation in plant heavy metal stress tolerance.
Heavy metal contamination is a major environmental constraint that negatively affects plant growth, metabolism, and agricultural productivity. Excess metals such as cadmium, lead, and copper disturb cellular functions mainly by inducing oxidative stress, disrupting nutrient balance, and causing toxicity at multiple levels of organization. To cope with these stresses, plants activate complex defense systems, among which melatonin (MT) (N-acetyl-5-methoxytryptamine) has recently emerged as a key regulatory molecule. This review highlights MT's central role in coordinating plant responses to heavy metal stress. MT strengthens redox homeostasis by enhancing both enzymatic and non-enzymatic antioxidant systems, thereby reducing reactive oxygen species (ROS) accumulation and limiting oxidative damage to cellular components. In addition to its antioxidant function, MT regulates metal uptake, transport, and sequestration by modulating transporter families such as NRAMP, ZIP, and HMA, while also promoting detoxification through phytochelatin (PC) and metallothionein (MT) pathways. MT also plays an important role in hormonal crosstalk, interacting with abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) signaling pathways to fine-tune stress perception and downstream defense responses. Furthermore, recent multi-omics studies have shown that MT induces broad transcriptional, proteomic, and metabolomic reprogramming, leading to coordinated adjustments in gene expression, protein activity, and metabolic pathways under heavy metal stress. Overall, MT functions as a central signaling hub that integrates redox regulation, hormonal signaling, and multi-omics networks to enhance plant tolerance to heavy metal stress. These insights deepen understanding of plant stress biology and offer promising strategies to improve crop resilience and phytoremediation efficiency in contaminated environments.