ATM1, an essential conserved transporter in Apicomplexa, bridges mitochondrial and cytosolic [Fe-S] biogenesis

Deepti Shrivastava1,2, Ernest Abboud3, Jadhav Prasad Ramchandra1

  • 1Division of Biochemistry and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India.

Plos Pathogens
|September 30, 2024
PubMed

Insights

This study identifies a crucial transporter, TgATM1, essential for iron-sulfur cluster transfer in Apicomplexa parasites. Its depletion impacts cytosolic protein assembly, highlighting a new target for antiparasitic drug development.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • Apicomplexa parasites cause severe human diseases.
  • Iron-sulfur ( [Fe-S] ) cluster biogenesis is vital for parasite survival.
  • The transporter linking mitochondrial [Fe-S] to cytosolic pathways was unknown in Apicomplexa.

Purpose of the Study:

  • Identify and characterize the ABC transporter responsible for [Fe-S] transfer in Apicomplexa.
  • Elucidate the role of this transporter in parasite viability and metabolism.
  • Investigate its function in clinically relevant parasites like Toxoplasma gondii and Plasmodium falciparum.

Main Methods:

  • Genetic manipulation (depletion of TgATM1).
  • Proteomic analysis to identify interacting proteins.
  • Functional complementation assays using yeast homologs.
  • Biochemical characterization of PfATM1.

Main Results:

  • TgATM1 depletion did not impair mitochondrial metabolism but affected cytosolic [Fe-S] protein assembly.
  • TgATM1 expression inversely correlated with proteins involved in [Fe-S] transfer to the outer mitochondrial membrane.
  • PfATM1 was confirmed as a functional ABC transporter modulated by GSSG and [4Fe-4S] clusters.

Conclusions:

  • The identified ABC transporter (TgATM1/PfATM1) is critical for inter-organelle [Fe-S] transport in Apicomplexa.
  • This transporter represents a potential target for novel antiparasitic therapies.
  • Understanding this pathway is key to developing new treatments against Apicomplexa-borne diseases.

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