Abstract

Distinct Arabidopsis thaliana ecotypes differ in humidity adaptation, with Tibet ecotype adapted to arid habitats exhibiting lower submergence tolerance than humidity-adapted counterparts. Here, we identify a unique 332-bp transposable element (TE) insertion in the promoter of HYDROGEN-PEROXIDE-INDUCED Ca 2+ INCREASES 1 ( HPCA1 ) specific to the Tibet ecotype. This insertion upregulates HPCA1 expression by the recruitment of active histone modifications. HPCA1, in turn, negatively regulates submergence tolerance through its interaction with VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3), a voltage-dependent ionic channel localized in the mitochondrial outer membrane. Transcriptomic analyses indicate that the HPCA1–VDAC3 module modulates submergence tolerance, at least in part, by regulating RBOHD , WRKY46 , and MYC2 to maintain reactive oxygen species (ROS) homeostasis. Additionally, HPCA1 facilitates VDAC3 phosphorylation and inhibits antioxidant enzyme activities, potentially disrupting ROS balance. A negative correlation between HPCA1 expression levels and precipitation is observed across global A. thaliana ecotypes. Together, our results suggest that the HPCA1–VDAC3 module integrates H 2 O 2 signaling and ROS homeostasis via regulation of RBOHD , WRKY46 , and MYC2 , thereby mediating a trade-off in humidity adaptation in A. thaliana and providing insights for breeding flooding-tolerant crops.