{
  "abstract": "In Drosophila, Arginine kinase 1 (Argk1) is involved in maintaining ATP homeostasis during bursts of activity in tissues with high and variable rates of energy turnover such as muscle. However, its role beyond stress conditions is less understood. Argk1 is the sole phosphagen kinase with dynamic expression throughout flight muscle development. Here, we show that at least one of the Argk1 isoforms localizes to mitochondria in the developing myofibers, and its function is also necessary for proper flight muscle development. Depleting Argk1 specifically in the muscles lead to low ATP level and NAD + /NADH ratio, indicative of defects in energy homeostasis, and results in animal lethality. In the wing disc-associated myoblasts, Argk1 knockdown causes a reduction in cell size without changes in cell cycle progression. Single cell RNA-sequencing (scRNA-seq) revealed that the transcriptomes of undifferentiated and differentiating Argk1-depleted myoblasts are not significantly affected compared to control. Furthermore, based on the marker expression and overall composition of scRNA-seq cell clusters, the early states of myoblasts differentiation are not severely disrupted in Argk1-depleted myoblasts. Nonetheless, Argk1 knockdown severely impacts later stages of muscle development. Remarkably, Argk1-depleted muscles completely lack spontaneous muscle contractions, which are required for proper sarcomere maturation in the formation of the indirect flight muscle. Accordingly, Argk1-depleted muscles showed defects related to sarcomere maturation, and mitochondrial morphogenesis; thus, leading to a severe reduction in muscle growth. Therefore, our data reveal an essential role for Argk1 in flight muscle development, presumably by sustaining local ATP levels to meet the energetic demand to support myofibrillogenesis, muscle growth and proper flight muscle function. Author summary: Phosphagen kinases, such as creatine kinases, maintain ATP levels during periods of high energy demand, such as muscle contractions, and thus play a key role in cellular energy homeostasis. In vertebrates, defects caused by the loss of creatine kinase are linked to diseases, including heart failure and muscular dystrophy. In Drosophila, the sole gene encoding a phosphagen kinase that is highly expressed in the muscles is Arginine kinase 1 (Argk1). It was previously shown that Argk1 is required to rapidly regenerate ATP to support high metabolic demand during the burst firing in motoneurons. Yet, its function during muscle development remains largely unexplored. Here, we uncover that Argk1 is implicated in the spontaneous contractions of the indirect flight muscles, a process that is associated with proper sarcomere maturation, which is tightly coordinated with mitochondrial morphogenesis. Altogether, our data reveal a role for Argk1 in energy homeostasis at the onset of myofibrillogenesis that is required for proper flight muscle development.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maria Paula Zappia"
    },
    {
      "name": "Anton Westacott"
    },
    {
      "name": "Hannah Cooke"
    },
    {
      "name": "Rhianna Geary"
    },
    {
      "name": "Libby Travers"
    },
    {
      "name": "Lucia de Castro"
    },
    {
      "name": "Oliver Carty"
    },
    {
      "name": "Maxim V. Frolov"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/79sx8gqzczjgz.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pgen.1012304",
  "fulltext_url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012304",
  "id": "79sx8gqzczjgz",
  "issns": [
    "1553-7404"
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  "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",
      "1312|Muscle Physiology and Disorders"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Myofibrils"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Myofibrils/Sarcomeres"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Bioenergetics/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Energy-producing organelles/Mitochondria"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Muscle cells/Myofibrils"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Muscle cells/Myofibrils/Sarcomeres"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Stem cells/Myoblasts"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Morphogenesis/Muscle differentiation"
    ],
    [
      "plos",
      "/Biology and life sciences/Developmental biology/Organism development/Organogenesis/Muscle development"
    ],
    [
      "plos",
      "/Biology and life sciences/Physiology/Muscle physiology/Muscle contraction"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Myofibrils"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Biological tissue/Muscle tissue/Muscle cells/Myofibrils/Sarcomeres"
    ],
    [
      "plos",
      "/Research and analysis methods/Specimen preparation and treatment/Staining/Nuclear staining/DAPI staining"
    ]
  ],
  "openalex": "W7213462672",
  "pdf_url": "https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1012304&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/79sx8gqzczjgz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pgen.1012304",
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      "url": "https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012304"
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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    {
      "field": "biology",
      "origin": "plos:stem cells",
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "Arginine Kinase 1 supports energy homeostasis in Drosophila flight muscle development",
  "title_text": "Arginine Kinase 1 supports energy homeostasis in Drosophila flight muscle development",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/79sx8gqzczjgz",
  "venue": "PLOS Genetics",
  "versions": []
}