Arginine Kinase 1 supports energy homeostasis in Drosophila flight muscle development
- 1Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois, United States of America
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.
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BibTeX
@article{zappia2026arginine,
title = {{Arginine Kinase 1 supports energy homeostasis in Drosophila flight muscle development}},
author = {Maria Paula Zappia and Anton Westacott and Hannah Cooke and Rhianna Geary and Libby Travers and Lucia de Castro and Oliver Carty and Maxim V. Frolov},
journal = {PLOS Genetics},
year = {2026},
month = sep,
doi = {10.1371/journal.pgen.1012304},
url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012304},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Arginine Kinase 1 supports energy homeostasis in Drosophila flight muscle development
AU - Maria Paula Zappia
AU - Anton Westacott
AU - Hannah Cooke
AU - Rhianna Geary
AU - Libby Travers
AU - Lucia de Castro
AU - Oliver Carty
AU - Maxim V. Frolov
PY - 2026
DA - 2026/09/17
JO - PLOS Genetics
DO - 10.1371/journal.pgen.1012304
UR - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012304
AB - 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.
SN - 1553-7404
ER -