Oxygen sensing in plants: from dynamic hypoxia signalling to the expanding roles of the Cysteine N-degron pathway

Recent discoveries have fundamentally transformed the paradigm of plant oxygen sensing. Hypoxia is no longer viewed solely because of environmental stress, such as flooding, but as a dynamic, intrinsic physiological signal that actively controls normal plant development. At the molecular level, this homeostatic oxygen monitoring is orchestrated by the Cysteine branch of the N-degron (Cys-N-degron) pathway. PLANT CYSTEINE OXIDASES (PCOs) act as direct oxygen sensors, using molecular oxygen as a co-substrate to oxidise N-terminal cysteine residues in Met-Cys (MC)-initiating proteins. This modification leads to their subsequent arginylation and proteasomal degradation via the E3 ligase PROTEOLYSIS 6 (PRT6). In addition to the well-studied group VII ETHYLENE RESPONSE FACTORS (ERFVIIs), the Cys-N-degron pathway substrate repertoire now encompasses critical developmental and epigenetic regulators, including VERNALIZATION 2 (VRN2) and LITTLE ZIPPER 2 (ZPR2). These targets selectively accumulate in naturally hypoxic microenvironments, such as the shoot apical meristem (SAM), where endogenous oxygen gradients function as positional cues to coordinate organogenesis and developmental phase transitions. Although the Arabidopsis thaliana reference proteome harbours 283 MC-proteins, the MC motif is necessary but not sufficient for turnover. Thus, structural, biochemical, and metabolic constraints determine substrate selectivity. Furthermore, analysis of 1,135 natural Arabidopsis accessions highlights substantial variation in the MC-protein landscape, driven by accession-specific motif gains and losses. Collectively, these insights bridge classical hypoxia stress responses with developmental signalling in plants.