From signal perception to adaptive responses: A comprehensive review of plant mechanisms under cadmium, lead, and aluminum stress

Heavy metals (HMs), pollutants produced by humans, significantly impact crop yields. The contamination of soil and water by HMs poses a serious environmental challenge. Although HMs naturally occur in the soil as rare elements, agricultural practices, refuse dumping, metallurgy, and manufacturing contribute to their environmental spread in higher concentrations that lead to negative effects on crop plants and human health. Even at low concentrations, HMs, such as cadmium (Cd), lead (Pb), and aluminum (Al), adversely impact root uptake and transport to vegetative and reproductive organs, disrupting mineral nutrition and homeostasis, which in turn influence the growth and development of both plant shoots and roots. Plants absorb HMs from contaminated soil or water, which inhibits root growth, causes leaf chlorosis, hinders stomatal opening, and can lead to wilting or death. Additionally, it suppresses photosynthesis and transpiration, induces oxidative stress, alters enzyme activity, and modifies gene expression. Resource allocation between growth and defense is a key trade-off for plant survival and fitness. Under heavy metal exposure, stronger defense responses often coincide with reduced growth, even without visible damage. Plants have evolved complex signaling networks that respond to environmental stimuli through signaling proteins, such as plasma membrane receptors and ion transporters, as well as cascades of kinases and other enzymes, ultimately leading to the activation of effectors. In the plant response to HMs stress, the pivotal signaling role is played by hormones and many additional compounds, including second messengers such as cytosolic Ca^2 + , reactive oxygen species (ROS), reactive nitrogen species (RNS), and cyclic nucleotides such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Moreover, it has recently been demonstrated that nucleotides such as exogenous ATP (eATP) can also play signaling roles in plant cells. These are part of the regulatory network, involving MAP kinase, SnRK, and transcription factors, that leads to the synthesis of metabolites capable of mitigating plant stress caused by HMs. Their uptake triggers diverse epigenetic mechanisms that may either promote or hinder plant stress tolerance. In response to HMs exposure, plants adjust gene expression through DNA methylation, histone acetylation, and microRNA-mediated gene silencing. Recent findings also highlight the involvement of epigenetic mechanisms as important post-transcriptional regulators within this signaling network, further fine-tuning plant responses to HMs. However, more research is still needed to identify the signaling networks involved in this process. This review summarizes the current understanding of perception, signal transduction, and plant responses to Cd, Pb, and Al stress.