Physiological and metabolic reprogramming under stress combination in plants

In nature, plants are rarely challenged by a single, isolated, environmental stress factor. Instead, they continuously experience a dynamic range of abiotic and biotic constraints, generating conditions of multifactorial stress combination (MFSC). Driven by anthropogenic activities, many stressors are increasing in their frequency, intensity, and duration, exposing plants to complex conditions that go well beyond two interacting factors. A recent conceptual advance is the recognition that plant responses to MFSC cannot be predicted by simply summing up plant responses of the different individual stresses that compose the MFSC. Rather, MFSC elicits novel plant physiological, transcriptomic, and metabolic states. This review synthesizes recent progress in understanding how MFSCs reshape plant physiology and metabolism. Specifically, it addresses the immense complexity of interactions extending beyond two stress factors, highlighting scenarios involving MFSCs acting either simultaneously or sequentially. By examining stomatal dynamics, hierarchical stress codes, and the integration of antagonistic cellular signals, this review outlines how physiological bottlenecks drive metabolic reprogramming. Ultimately, this review aims to clarify the sophisticated linkages between whole-plant physiology and molecular metabolism under MFSCs, as well as to identify current priorities for translating this deep biological understanding into actionable strategies for breeding climate-resilient crops.