Abstract
Sphingosine-1-phosphate is a signaling molecule involved in the control of cell migration, differentiation, survival and other physiological processes. This sphingolipid metabolite can be degraded by the action of sphingosine-1-phosphate lyase (SPL) to form hexadecenal and ethanolamine phosphate. The importance of SPL-mediated ethanolamine phosphate formation has been characterized in only few cell types. We show that in the protozoan parasite Trypanosoma brucei, expression of TbSpl is essential for cell survival. Ablation of TbSpl expression increased sphingosine-1-phosphate levels and reduced de novo formation and steady-state levels of the glycerophospholipid phosphatidylethanolamine (PE). Growth of TbSpl-depleted parasites could be in part rescued by ethanolamine supplementation to the growth medium, indicating that the main function of TbSpl is to provide ethanolamine phosphate for PE synthesis. In contrast to most cell types analyzed, where SPL localizes to the endoplasmic reticulum, we found by high-resolution microscopy that TbSpl is a mitochondrial protein. In spite of its mitochondrial localization, TbSpl depletion had no apparent effect on mitochondrial morphology but resulted in aggregation of acidocalcisomes. Our results link mitochondria to sphingolipid metabolism and suggest possible roles for PE in acidocalcisome function.