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Sphingolipids are a diverse group of lipids recognized as important components of cellular membranes and regulators of processes during development and in response to environmental stresses. Serine palmitoyltransferase (SPT) catalyzes the first step in sphingolipid biosynthesis and is a primary regulatory point for homeostasis. ORM proteins have been identified as negative regulators of SPT activity, however the mechanistic details of the regulation are only beginning to be understood. In this work, we show that ORM1 and ORM2 are essential for life cycle completion in Arabidopsis thaliana. Furthermore, the study of a structural ORM1 variant provided information about a transmembrane domain involved in the interaction with SPT. We also provide insights into the physiological effects caused by mutations in SPT that induce the production of deoxysphingolipids. Our research demonstrates that plants expressing these mutations showed early senescence and reduced sensitivity to the cell death induced by Fumonisin B1. These findings suggest functional roles of deoxysphingolipids that have not been explored in plants. Finally, we describe a labeling approach to build a sphingolipid kinetic model to study the metabolic flux of sphingolipids during pathogen infection. This study considers a more comprehensive view of the sphingolipid metabolic network that changes dynamically when perturbed.
Advisor: Edgar Cahoon