A mechanistic integration of hypoxia signaling with energy, redox, and hormonal cues

Oxygen deficiency (hypoxia) occurs naturally in many developing plant tissues but can become a major threat during acute flooding stress. Consequently, plants as aerobic organisms must rapidly acclimate to hypoxia and the associated energy crisis to ensure cellular and ultimately organismal survival. In plants, oxygen sensing is tightly linked with oxygen-controlled protein stability of group VII ETHYLENE-RESPONSE FACTORs (ERFVII), which, when stabilized under hypoxia, act as key transcriptional regulators of hypoxia-responsive genes (HRGs). Multiple signaling pathways feed into hypoxia signaling to fine-tune cellular decision-making under stress. First, ATP shortage upon hypoxia directly affects the energy status and adjusts anaerobic metabolism. Secondly, altered redox homeostasis leads to reactive oxygen and nitrogen species (ROS and RNS) accumulation, evoking signaling and oxidative stress acclimation. Finally, the phytohormone ethylene promotes hypoxia signaling to improve acute stress acclimation, while hypoxia signaling in turn can alter ethylene, auxin, abscisic acid, salicylic acid, and jasmonate signaling to guide development and stress responses. In this Update, we summarize the current knowledge on how energy, redox, and hormone signaling pathways are induced under hypoxia and subsequently integrated at the molecular level to ensure stress-tailored cellular responses. We show that some HRGs are responsive to changes in redox, energy, and ethylene independently of the oxygen status, and we propose an updated HRG list that is more representative for hypoxia marker gene expression. We discuss the synergistic effects of hypoxia, energy, redox, and hormone signaling and their phenotypic consequences in the context of both environmental and developmental hypoxia.