Bretscher, H.; O'Connor, M. B.

Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in both nuclear and mitochondrial DNA (mtDNA). We show that motoneuron to muscle signaling by the TGFbeta/Activin family member Actbeta positively regulates glycogen levels during Drosophila development. Remarkably, we find that levels of stored glycogen are unaffected by altering cytoplasmic glucose catabolism. Instead, Actbeta loss reduces levels of mtDNA and nuclearly encoded genes required for mtDNA replication, transcription and translation. Direct RNAi mediated knockdown of these same nuclearly encoded mtDNA expression factors also results in decreased glycogen stores. Lastly, we find that expressing an activated form of the type I receptor Baboon in muscle restores both glycogen and mtDNA levels in actbeta mutants, thereby confirming a direct link between Actbeta signaling, glycogen homeostasis and mtDNA expression factors.