Mechanical activation of mitochondrial energy metabolism during cell differentiation

In multicellular lives, differentiation of many types of stem and progenitor cells is often accompanied by a metabolic transition from glycolysis to mitochondrial oxidative phosphorylation. The mechanisms driving this metabolic transition in vivo are largely unknown. Here, we show that, during differentiation of the Drosophila female germline cyst, the surrounding somatic cells compress the cyst and increase the tension of cyst cells’ membranes. Transmembrane channel-like, an evolutionarily conserved ion channel involved in mechanosensation, maintains cytosolic Ca2+ levels in compressed differentiating cysts. Cytosolic Ca2+ induces transcriptional activation of oxidative phosphorylation through a CaMKI-Fray-JNK signaling relay. Our findings demonstrate a molecular link between cell mechanics and mitochondrial energy metabolism, with implications in other developmentally orchestrated metabolic transitions in mammals. One-Sentence Summary Mechanical forces from the surrounding tissue activate mitochondrial energy metabolism in differentiating cells in vivo. ### Competing Interest Statement The authors have declared no competing interest.