Fig. 8: The working model of mtROS-induced CRC development. | Nature Communications

Fig. 8: The working model of mtROS-induced CRC development.

From: ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3

Fig. 8

In normal intestinal epithelial cells (left panel), PGAM5 resides within mitochondria, leading to increase in pMST3. Elevated pMST3 promotes YAP phosphorylation through STK25-LATS axis, and enhances its subsequent ubiquitination and degradation. In colorectal cancer cells (right panel), PGAM5 undergoes cleavage and become released into the cytoplasm by sensing elevated levels of mtROS. Cytosolic PGAM5 dephosphorylates MST3 to activate YAP signalling by suppressing STK25-mediated LATS phosphorylation, which promotes CRC growth and metastasis. In turn, MST3 inactivation gives rise to reduced mitochondrial membrane potential, that induces PGAM5 cleavage. This reveals a positive feedback loop machinery of PGAM5 cleavage and MST3 inactivation in promoting CRC progression.

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