Related Experiment Video
Updated: Jun 11, 2025

Isolation of F1-ATPase from the Parasitic Protist Trypanosoma brucei
Published on: January 22, 2019
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.
Abstract:
The Apicomplexa phylum encompasses numerous obligate intracellular parasites, some associated with severe implications for human health, including Plasmodium, Cryptosporidium, and Toxoplasma gondii. The iron-sulfur cluster [Fe-S] biogenesis ISC pathway, localized within the mitochondrion or mitosome of these parasites, is vital for parasite survival and development. Previous work on T. gondii and Plasmodium falciparum provided insights into the mechanisms of [Fe-S] biogenesis within this phylum, while the transporter linking mitochondria-generated [Fe-S] with the cytosolic [Fe-S] assembly (CIA) pathway remained elusive. This critical step is catalyzed by a well-conserved ABC transporter, termed ATM1 in yeast, ATM3 in plants and ABCB7 in mammals. Here, we identify and characterize this transporter in two clinically relevant Apicomplexa. We demonstrate that depletion of TgATM1 does not specifically impair mitochondrial metabolism. Instead, proteomic analyses reveal that TgATM1 expression levels inversely correlate with the abundance of proteins that participate in the transfer of [Fe-S] to cytosolic proteins at the outer mitochondrial membrane. Further insights into the role of TgATM1 are gained through functional complementation with the well-characterized yeast homolog. Biochemical characterization of PfATM1 confirms its role as a functional ABC transporter, modulated by oxidized glutathione (GSSG) and [4Fe-4S].
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.
Related Concept Videos
The ADP/ATP Carrier Protein
Protein Transport into the Inner Mitochondrial Membrane
Transport of mitochondrial precursors across the TIM23 channel is driven by...
ATP Synthase: Mechanism
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
The Inner Mitochondrial Membrane
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...

