Arginine Kinase 1 regulates energy homeostasis in Drosophila muscle development

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. Here, we show that Argk1 maintains energy homeostasis during flight muscle development and is required for animal viability and proper muscle function. The knockdown of Argk1 causes defects in both early and late stages of myogenesis. In the proliferating myoblasts associated with the wing disc, Argk1 depletion results in a reduction in cell size without changes in cell cycle progression. Single cell RNA-sequencing revealed that the overall composition of differentiating and undifferentiating myoblasts is not altered. Nonetheless, Argk1 knockdown causes broad alterations in the expression of genes involved in various metabolic pathways. This correlates with low levels in both ATP content and NAD+/NADH ratio. Later in muscle development, Argk1-depleted muscles completely lack spontaneous muscle contractions that are essential in myofibrillogenesis. Accordingly, Argk1 knockdown results in severe defects in sarcomere structure, while the mitochondrial network is highly fragmented. Furthermore, muscle growth is severely reduced. Thus, our data reveal an essential role for Argk1 in maintaining energy homeostasis throughout muscle development, which is required to meet the demand to support myofibrillogenesis, muscle growth and proper muscle function.