Ali Raza, Yiran Li, Mengkai Zhao, Tao Ming, Rodomiro Ortíz, Robert J. Henry, Zhangli Hu
Plants in natural environments often encounter multifactorial abiotic stress combinations that trigger regulatory responses distinct from those triggered by individual stresses. Traditional single-stress paradigms inadequately capture these complex interactions, limiting crop improvement efforts. Here, we discuss how plants integrate conserved signaling pathways with combination-specific regulatory modules (CSRMs) across multiple regulatory layers to mediate stress tolerance. Using recent findings, including the identification of specific transcription factor complexes that decode unique stress combinations, we highlight how CSRMs coordinate downstream protective pathways such as reactive oxygen species buffering. These insights suggest a multi-layered regulatory logic underlying plant adaptation to combined stresses. Leveraging CSRMs through integrative discovery and engineering approaches offers a promising avenue for developing climate-smart crops with potentially enhanced and stable tolerance under unpredictable field conditions.