A dual role of Arabidopsis PAL nuclear localization in fine tuning flavonoid biosynthesis.

The phenylpropanoid pathway is essential for plant development and environmental adaptation, producing metabolites such as flavonoids, lignin, and salicylic acid. Phenylalanine ammonia-lyase (PAL) catalyzes the first committed step in this pathway and has long been viewed as a cytoplasmic enzyme. Here, we reveal that PAL responds to elevated flavonoid levels in Arabidopsis by undergoing phosphorylation and relocating to the nucleus. Nuclear sequestration of PAL reduces its cytoplasmic abundance and enzymatic activity, resulting in rapid suppression of phenylpropanoid metabolic flux. In parallel, nuclear-localized PAL interacts with the transcription factor TT8, disrupting MBW complex formation and down-regulating flavonoid biosynthetic genes. This dual mechanism enables PAL to act as a metabolic feedback regulator that dynamically adjusts flavonoid production in response to internal metabolic states. Our findings redefine PAL as both a biosynthetic enzyme and a responsive integrator of cellular metabolic status, establishing a previously unknown paradigm for feedback control in plant specialized metabolism.