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Peer-reviewedCC BY-NC-ND 4.0Nature Communications

A global S-palmitoylation map of Trypanosoma cruzi identifies ABCA10 as a key component of a redundant heme-acquisition system

  • Gonzalo Seminario-Mondejar1,2
  • Menna Etheridge1,2
  • Anthony A. Ruberto3
  • Susan Phan2
  • Julia Alejandra Cricco4,5
  • Ronald Drew Etheridge1,2
5 affiliations
  1. 1Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA USA
  2. 2Department of Cellular Biology, University of Georgia, Athens, GA USA
  3. 3Department of Biomedical Sciences, Florida State University, Tallahassee, FL USA
  4. 4Instituto de Biología Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-Universidad Nacional de Rosario (UNR), Rosario, Argentina
  5. 5Área Biofísica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario (UNR), Rosario, Argentina
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Abstract

Survival and transmission of the human pathogen Trypanosoma cruzi depend on dynamic remodeling of its membrane proteome, yet the post-translational networks governing this plasticity remain obscure. Using metabolic labeling and quantitative mass spectrometry, we present a comprehensive map of the T. cruzi S-palmitoylome: a high-confidence atlas of 254 proteins enriched for signaling factors, cytoskeletal regulators, and membrane transporters. Functional screening with our aptazyme-based SHARK knockdown system identifies ABCA10, an uncharacterized ABC transporter central to heme homeostasis. Depletion of ABCA10 triggers a compensatory surge in cytostome-mediated endocytosis, rendering this normally dispensable process conditionally essential. ABCA10 expression is itself heme-regulated and upon heme starvation it redistributes from the flagellar pocket to pre-lysosomal reservosomes. We further show that endocytosis is directly tuned by extracellular heme, placing the entire uptake apparatus, not only ABCA10, under heme-responsive control. Together, these findings reveal a redundant heme-scavenging strategy and expose a druggable vulnerability in a neglected pathogen.

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Cite

BibTeXRIS
BibTeX
@article{seminariomondejar2026global,
  title = {{A global S-palmitoylation map of Trypanosoma cruzi identifies ABCA10 as a key component of a redundant heme-acquisition system}},
  author = {Gonzalo Seminario-Mondejar and Menna Etheridge and Anthony A. Ruberto and Susan Phan and Julia Alejandra Cricco and Ronald Drew Etheridge},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77828-y},
  url = {https://doi.org/10.1038/s41467-026-77828-y},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - A global S-palmitoylation map of Trypanosoma cruzi identifies ABCA10 as a key component of a redundant heme-acquisition system
AU  - Gonzalo Seminario-Mondejar
AU  - Menna Etheridge
AU  - Anthony A. Ruberto
AU  - Susan Phan
AU  - Julia Alejandra Cricco
AU  - Ronald Drew Etheridge
PY  - 2026
DA  - 2026/09/24
JO  - Nature Communications
DO  - 10.1038/s41467-026-77828-y
UR  - https://doi.org/10.1038/s41467-026-77828-y
AB  - Survival and transmission of the human pathogen Trypanosoma cruzi depend on dynamic remodeling of its membrane proteome, yet the post-translational networks governing this plasticity remain obscure. Using metabolic labeling and quantitative mass spectrometry, we present a comprehensive map of the T. cruzi S-palmitoylome: a high-confidence atlas of 254 proteins enriched for signaling factors, cytoskeletal regulators, and membrane transporters. Functional screening with our aptazyme-based SHARK knockdown system identifies ABCA10, an uncharacterized ABC transporter central to heme homeostasis. Depletion of ABCA10 triggers a compensatory surge in cytostome-mediated endocytosis, rendering this normally dispensable process conditionally essential. ABCA10 expression is itself heme-regulated and upon heme starvation it redistributes from the flagellar pocket to pre-lysosomal reservosomes. We further show that endocytosis is directly tuned by extracellular heme, placing the entire uptake apparatus, not only ABCA10, under heme-responsive control. Together, these findings reveal a redundant heme-scavenging strategy and expose a druggable vulnerability in a neglected pathogen.
SN  - 2041-1723
ER  -