Ferroptosis contributes to developmental cell death in rice blast

We identified that ferroptosis, an iron-dependent non-apoptotic cell death process, occurs in the rice blast fungus Magnaporthe oryzae, and plays a key role in infection-related development therein. Ferroptosis in the blast fungus was confirmed based on the four basic criteria. We confirmed the dependence of ferroptosis on ferric ions, and optimized C11-BODIPY581/591 as a key sensor for subcellular detection and quantification of lipid peroxides that mediate ferroptotic cell death during the pathogenic growth phase of M. oryzae. In addition, we uncovered an important regulatory function for reduced glutathione and the NADPH oxidases in generating/modulating the superoxide moieties for ferroptotic cell death in Magnaporthe. Ferroptosis was found to be necessary for the specific developmental cell death in conidia during appressorium maturation in rice blast. Such ferroptotic cell death initiated first in the terminal cell and progressed sequentially to the entire conidium. Chelation of iron or chemical inhibition of ferroptosis caused conidial cells to remain viable and led to strong defects in host invasion by M. oryzae. Precocious induction of ferroptosis in a blast-susceptible rice cultivar led to resistance against M. oryzae invasion. Interestingly, ferroptosis and autophagy were found to play inter-reliant or codependent roles in contributing to such precise cell death in M. oryzae conidia during pathogenic differentiation. Our study provides significant molecular insights into understanding the role of developmental cell death and iron homeostasis in infection-associated morphogenesis and in fungus-plant interaction in the blast pathosystem.