Control of Mitochondrial Dynamics by Dpgc1 Limits Yorkie-induced Oncogenic Growth in Drosophila

Mitochondrial function and dynamics are crucial for maintaining cellular homeostasis and overall health. Disruptions in these processes can lead to various diseases, including cancer. The Hippo signaling pathway, a universal growth regulator, plays central roles in cancer through its main effector, the Yes-associated protein (YAP), known as Yorkie (Yki) in Drosophila. Yki upregulation drives benign tissue overgrowth in Drosophila imaginal discs. Our research demonstrates that the conserved metabolic regulator dPGC1 limits Yki-driven tissue hyperplasia and maintains tissue homeostasis in vivo. Yki upregulation and dPGC1 depletion lead to tumors characterized by enlarged and hyperfused mitochondria, a condition both necessary and sufficient for Yki-driven oncogenic growth. Our findings demonstrate that mitochondrial hyperfusion elevates the levels of the cell cycle regulator Cyclin E, which is crucial for tumor development. Our findings identify dPGC1 as a context-dependent tumor suppressor that coordinates mitochondrial dynamics and cell cycle regulation in response to oncogene activation. Defects in these processes are commonly found in cancer cells, highlighting major implications for cancer development in humans. ### Competing Interest Statement The authors have declared no competing interest.