After successful double fertilization, ZmMYB98 and its associated gene regulatory network (GRN) are downregulated, while a GRN is activated leading to RALF12 signaling culminating in high levels of mitochondrial ROS accumulation at the filiform apparatus adjacent region, oxidative stress, mitophagy, and synergid apoptosis. Activated ethylene biosynthesis further promotes sensitized synergid cell death. RALF12-mediated mitochondrial oxidative stress and ethylene biosynthesis can individually trigger synergid cell death, while they work synergistically to efficiently activate PCD TFs and PCD executors for persistent synergid nucleus and whole-cell elimination. Vacuole rupture as well as cell intercalation mediated by VPE and CEP1 likely contribute to synergid-endosperm (SE) fusion.