A bridge-like lipid transfer protein is critical for generation of invasive stages in malaria parasites

TL;DR

This study identifies a lipid transfer protein critical for the formation of invasive stages in malaria parasites by facilitating lipid transfer from the ER to a key organelle.

Contribution

The study reveals PfVPS13L1 as a bridge-like lipid transfer protein essential for malaria parasite development.

Findings

PfVPS13L1 bridges the ER with the inner membrane complex (IMC) in malaria parasites.

Loss of PfVPS13L1 impairs IMC growth and schizogony, reducing parasite progeny.

The protein mediates bulk lipid transfer required for invasive stage formation.

Abstract

Malaria blood stages build and maintain an intricate system of membranes during their cycle of rapid growth and schizogony (daughter-cell formation), requiring precise mechanisms of lipid synthesis and trafficking. Lipid transfer proteins (LTPs) at ER membrane contact sites (MCSs) have emerged as key for lipid distribution processes but remain largely unexplored in protozoans. Here we use the ER adapter VAP to identify essential mechanisms of lipid transfer at ER-MCSs in P. falciparum. One PfVAP-interacting LTP is the bridge-like PfVPS13L1, which allows bulk flow of lipids between two apposed membranes. PfVPS13L1 bridges the ER with the nascent inner membrane complex (IMC), a de novo-generated organelle required for schizogony. Its loss-of-function reduces IMC growth and leads to smaller anucleated progeny, impairing schizogony. Our data supports a model in which VPS13L1 is critical for the formation of apicomplexan invasive stages by mediating bulk transfer of lipids from the ER to the growing IMC.

Organelle biogenesis in the rapidly growing malaria parasite requires extensive membrane genesis and remodeling. Here a mechanism to directly supply lipids from the ER to the inner membrane complex (IMC), a de novo formed organelle needed for progeny formation, is shown.

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