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<p>Apicomplexan parasites, including <i>Plasmodium falciparum</i> and <i>Toxoplasma gondii</i>, contain specialized secretory organelles such as micronemes, rhoptries, and dense granules, which are essential for parasite motility, host cell invasion, development, and egress. DedA superfamily proteins are implicated in lipid mobilization, which is a key requirement for organelle biogenesis. Herein, we identify and investigate the vacuole membrane protein 1 (VMP1), a DedA superfamily member, of <i>P. falciparum</i> (PfVMP1) and <i>T. gondii</i> (TgVMP1). PfVMP1 and TgVMP1 are ER-localized lipid scramblases. TgVMP1 depletion adversely affects parasite development, motility, host cell invasion, and egress. These phenotypes are consistent with impaired rhoptry and dense granule biogenesis, and decreased secretion of micronemes and rhoptries in TgVMP1-depleted parasites, indicating a crucial role for TgVMP1 in the biogenesis and function of these organelles. TgVMP1 depletion impairs lipid droplet homeostasis and ER organization, and causes loss of intravacuolar network in the parasitophorous vacuole, which are key for parasite development. Restoration of the ER-localized lipid scramblase by complementing TgVMP1-depleted parasites with PfVMP1 or a homolog as distant as human VMP1 rescues the depleted parasites, indicating their functional conservation and a crucial role for ER-resident lipid scramblase activity in the biogenesis and function of secretory organelles.</p>

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An ER-resident lipid scramblase is crucial for biogenesis and function of apicomplexan parasite secretory organelles

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月13日

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  • G. Srinivas Reddy,
  • Somesh M. Gorde,
  • Kanika Saxena,
  • Manash Kumar Behera,
  • Abhijit S. Deshmukh,
  • Puran Singh Sijwali

摘要

Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii, contain specialized secretory organelles such as micronemes, rhoptries, and dense granules, which are essential for parasite motility, host cell invasion, development, and egress. DedA superfamily proteins are implicated in lipid mobilization, which is a key requirement for organelle biogenesis. Herein, we identify and investigate the vacuole membrane protein 1 (VMP1), a DedA superfamily member, of P. falciparum (PfVMP1) and T. gondii (TgVMP1). PfVMP1 and TgVMP1 are ER-localized lipid scramblases. TgVMP1 depletion adversely affects parasite development, motility, host cell invasion, and egress. These phenotypes are consistent with impaired rhoptry and dense granule biogenesis, and decreased secretion of micronemes and rhoptries in TgVMP1-depleted parasites, indicating a crucial role for TgVMP1 in the biogenesis and function of these organelles. TgVMP1 depletion impairs lipid droplet homeostasis and ER organization, and causes loss of intravacuolar network in the parasitophorous vacuole, which are key for parasite development. Restoration of the ER-localized lipid scramblase by complementing TgVMP1-depleted parasites with PfVMP1 or a homolog as distant as human VMP1 rescues the depleted parasites, indicating their functional conservation and a crucial role for ER-resident lipid scramblase activity in the biogenesis and function of secretory organelles.