A lysophospholipase plays role in generation of neutral-lipids required for hemozoin formation in malaria parasite

Phospholipid metabolism is crucial for membrane dynamics in malaria parasites during entire cycle in the host cell. harbours several members of phospholipase family, which play key role in phospholipid metabolism. Here we have functionally characterized a parasite lysophospholipase (LPL1) with a view to understand its role in lipid homeostasis. We used a regulated fluorescence affinity tagging, which allowed endogenous localization and transient knock-down of the protein. fLPL1localizes to dynamic vesicular structures that traffic from parasite periphery, through the cytosol to get associated as a multi-vesicular neutral lipid rich body next to the food-vacuole during blood stages. Down-regulation of the LPL1 disrupted parasite lipid-homeostasis leading to significant reduction of neutral lipids in lipid-bodies. This hindered conversion of heme to hemozoin, leading to food-vacuole abnormalities, which in turn disrupted parasite development cycle and significantly inhibited parasite growth. Detailed lipidomic analyses of inducible knock-down parasites confirmed role of LPL1 in generation of neutral lipid through recycling of phospholipids. Our study thus suggests a specific role of LPL1 to generate neutral lipids in the parasite, which are essential for parasite survival.