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Melatonin has shown potent effects on improving plant stress resistance and phytoremediation upon HM stress, however, the systematic discussion of these extensive mechanisms and the gaps to practical applications remain elusive. This review aims to systemically provide the mechanistic understanding and environmental implication of melatonin integrative effects on alleviating HM toxicity. On the one hand, melatonin modulates HM homeostasis, induces HM detoxification, keeps photosynthesis and nutrient balance, and activates antioxidant defense systems to improve plant defense resistance to HM. On the other hand, melatonin triggers multiple transcriptional gene networks and extensive phytohormone crosstalks in plant defense responses. Notably, melatonin and melatonin\u2010producing microbes exhibit potential applications in keeping plant growth and improving phytoremediation under HM conditions, indicating their effects on plant\u2010microbiome\u2010soil synergistic feedbacks. Finally, the current challenges and future perspectives of melatonin integrative mechanisms and applications are elucidated, highlighting that basic scientific questions and combined technologies should be further integrated to promote its practical applications. In summary, this review clarifies the multifaceted mechanisms of melatonin\u2010integrated plant responses and potential remediation applications for environmental HMs, providing relative broad\u2010spectrum and long\u2010term strategies.<\/jats:p>","DOI":"10.1111\/jpi.70150","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:07:15Z","timestamp":1779800835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Melatonin\u2010Mediated Alleviation of Plant Response to Heavy Metals: From Integrative Mechanisms to Potential Applications"],"prefix":"10.1111","volume":"78","author":[{"given":"X.","family":"Cheng","sequence":"first","affiliation":[{"name":"Anhui Provincial Key Laboratory of Biodiversity Conservation and Characteristic Resource Utilization in Southwest Anhui, College of Life Science and Food Engineering Anqing Normal University Anqing 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