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

ABSTRACT: The survival and continued transmission of the human infecting parasite Trypanosoma cruzi depends on the dynamic remodeling of its membrane proteome, yet the post-translational networks governing this plasticity remain largely obscure. Here, we deployed metabolic labeling coupled with quantitative mass spectrometry to generate the first comprehensive S-palmitoylome of T. cruzi. We defined a high-confidence atlas of 254 S-palmitoylated proteins, revealing an enrichment in signaling factors, cytoskeletal regulators, and membrane transporters. Leveraging our aptazyme-based SHARK conditional knockdown system for scalable genetic screening, we validated palmitoylated candidates and uncovered a critical link between lipid signaling and nutrient acquisition. Our functional screen identified ABCA10, a previously uncharacterized ATP-binding cassette (ABC)-transporter, as central to heme homeostasis. Strikingly, depletion of ABCA10 triggered a massive compensatory surge in cytostome-mediated endocytosis, rendering this normally dispensable pathway conditionally essential for survival. We further demonstrate that ABCA10 is a heme-responsive transporter that dynamically redistributes from the flagellar pocket to lysosomal compartments upon heme starvation, exposing a redundant, multi-modal strategy for scavenging this essential cofactor. This study not only provides a foundational proteomic resource but also exposes a novel, druggable vulnerability at the intersection of lipid signaling and metabolic survival.

INSTRUMENT(S):

ORGANISM(S): Trypanosoma Cruzi

TISSUE(S): Cell Culture

SUBMITTER: Sophe Alvarez  

LAB HEAD: Sophie Alvarez

PROVIDER: PXD074013 | Pride | 2026-07-30

REPOSITORIES: Pride