Abstract Cellular development requires the integrated assembly of intracellular structures into functionally specialized regions supporting overall cellular performance. However, it remains unclear how coordination of organelle interactions contributes to development of functional specificity across cell types. Here, we utilize a subcellular connectomics approach to define the cell-scale reorganization of the mitochondria-organelle interactome across postnatal development in skeletal muscle. We show that while mitochondrial networks are disorganized and loosely associated with the contractile apparatus at birth, contact sites among mitochondria, lipid droplets, and the sarcoplasmic reticulum are highly abundant in neonatal muscles. The maturation process is characterized by a transition to highly organized mitochondrial networks wrapped tightly around the muscle sarcomere but also to less frequent interactions with both lipid droplets and the sarcoplasmic reticulum. These data demonstrate a developmental redesign reflecting a functional shift from muscle cell assembly supported by inter-organelle communication toward a muscle fiber highly specialized for contractile function.

Reorganization of the Mitochondria-Organelle Interactome during Postnatal Development in Skeletal Muscle