{
  "abstract": "Trypanosoma cruzi, the etiological agent of Chagas Disease (CD), represents a significant public health concern and serves as a valuable model for investigating the cell cycle in early-diverging eukaryotes. Its unique cellular features,including the absence of chromosome condensation and the coordination of nuclear division with specialized organelles, provide insights into non-canonical regulatory mechanisms, and underscore the pivotal role of the nucleus in maintaining genomic integrity and regulating fundamental processes such as DNA replication and gene expression. To investigate nuclear dynamics throughout the cell cycle, we synchronized T. cruzi epimastigotes at the G1/S transition using hydroxyurea (HU), followed their progression through S and G2/M phases, and quantitatively analyzed isolated nuclear proteins by LC-MS/MS. We identified 2,937 nuclear-enriched proteins, revealing distinct, phase-specific expression patterns. The G1/S phase was marked by increased levels of metabolic enzymes including those related to energy and nucleotide/nucleoside metabolisms. The S phase showed elevated abundance of canonical and variant histones, consistent with chromatin remodeling and DNA replication. The G2/M phase was enriched in proteins involved in protein synthesis and microtubule dynamics, essential for mitosis. Notably, metabolic enzymes represented approximately 6% of the proteins identified in the purified nuclear fraction, consistent with previously published proteomic analyses of T. cruzi nuclear-enriched fractions. Hexokinase, citrate synthase, and pyruvate kinase activities were detected in extracts from this fraction, while immunofluorescence supported the association of hexokinase and citrate synthase with the nuclear region. These results suggest that metabolic enzymes and/or their metabolites may modulate nuclear processes in T. cruzi, potentially influencing the epigenome and gene expression regulation, as proposed in other eukaryotic models. Altogether, our findings reveal dynamic remodeling of the nuclear proteome during the T. cruzi cell cycle and point to a previously underappreciated role for metabolic enzymes likely regulating nuclear functions in a cell cycle-dependent manner. Author summary: Chagas disease is caused by the parasite Trypanosoma cruzi. To multiply, this parasite must coordinate DNA replication, nuclear events, and the division of single-copy structures such as the kinetoplast and flagellum. While previous proteomic studies have provided comprehensive insights into the parasite’s proteome, the changes in nuclear protein composition that accompany cell-cycle progression remain largely unexplored. We addressed this by synchronizing epimastigotes at key cell cycle stages, isolating nuclei, and performing quantitative proteomic analysis. Our dataset revealed that the nuclear environment is highly dynamic: proteins involved in DNA packaging increased when the genome was being copied, whereas other proteins became more prominent as cells prepared to divide. A notable finding was the presence of cell cycle-regulated metabolic enzymes in nuclear preparations, despite their canonical localization in the cytoplasm, glycosome, or mitochondria. These enzymes were consistently detected in nuclear preparations and supported by comparisons with other proteomic resources, enzymatic activity assays, and immunofluorescence analyses of selected candidates, although further experimental validation will be necessary to establish the nuclear localization of individual proteins. Together, our results provide a detailed view of nuclear remodeling during parasite proliferation and suggest a potential connection between metabolic pathways and nuclear functions in T. cruzi.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Cell Cycle, Butantan Institute, São Paulo, Brazil",
    "Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil",
    "School of Infection & Immunity, University of Glasgow, Glasgow, United Kingdom",
    "Laboratory of Biochemistry of Tryps (LaBTryps), Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ana Paula Menezes"
    },
    {
      "affs": [
        1
      ],
      "name": "Camila Gachet-Castro"
    },
    {
      "affs": [
        2
      ],
      "name": "Suzanne McGill"
    },
    {
      "affs": [
        3
      ],
      "name": "Richard Burchmore"
    },
    {
      "name": "Ariel Silber"
    },
    {
      "name": "Maria Carolina Elias"
    },
    {
      "name": "Júlia P. C. da Cunha"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/emwcb41v3ggzz.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pntd.0013299",
  "fulltext_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013299",
  "id": "emwcb41v3ggzz",
  "issns": [
    "1935-2735"
  ],
  "landing_url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013299",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Trypanosoma species research and implications"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzyme chemistry/Enzyme metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Protein metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Proteomes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell physiology/Cell metabolism"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cell processes/Cell cycle and cell division"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Life cycles/Parasitic life cycles/Parasitic cell cycles"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Eukaryota/Protozoans/Parasitic protozoans/Trypanosoma/Trypanosoma cruzi"
    ],
    [
      "plos",
      "/Biology and life sciences/Parasitology/Parasitic life cycles/Parasitic cell cycles"
    ]
  ],
  "openalex": "W7214583101",
  "pdf_url": "https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0013299&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/emwcb41v3ggzz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pntd.0013299",
      "source": "plos",
      "url": "https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013299"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:enzymology",
      "subfield": "enzymology-metabolism"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Nuclear proteome analysis suggests spatial and temporal compartmentalization of metabolic enzymes during Trypanosoma cruzi cell cycle",
  "title_text": "Nuclear proteome analysis suggests spatial and temporal compartmentalization of metabolic enzymes during Trypanosoma cruzi cell cycle",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/emwcb41v3ggzz",
  "venue": "PLOS Neglected Tropical Diseases",
  "versions": []
}