Endoplasmic reticulum-mitochondrial calcium transport contributes to soft extracellular matrix-triggered mitochondrial dynamics and mitophagy in breast carcinoma cells

Here, we examined the relationship between substrate stiffness and mitochondrial dynamics by using polyacrylamide (PAA) substrates to simulate the stages of breast cancer or BAPN to reduce tumor tissue stiffness. The results elucidated that soft substrate triggered the recruitment of DRP1 and subsequent mitochondrial fission and mitophagy by ER-MITO calcium transport. Furthermore, mitophagy partly attenuated soft ECM-mediated tumor tissue necrosis and contributed to tumor survival in vivo. Our discoveries revealed the molecular mechanisms by which mechanical stimulation regulates mitochondrial dynamics, providing valuable insights into ECM stiffness as a target for anti-tumor approaches, which could be beneficial for both biomechanics research and clinical applications.

Here, we examined the relationship between substrate stiffness and mitochondrial dynamics by using polyacrylamide (PAA) substrates to simulate the stages of breast cancer or BAPN to reduce tumor tissue stiffness. The results elucidated that soft substrate triggered the recruitment of DRP1 and subsequent mitochondrial fission and mitophagy by ER-MITO calcium transport. Furthermore, mitophagy partly attenuated soft ECM-mediated tumor tissue necrosis and contributed to tumor survival in vivo. Our discoveries revealed the molecular mechanisms by which mechanical stimulation regulates mitochondrial dynamics, providing valuable insights into ECM stiffness as a target for anti-tumor approaches, which could be beneficial for both biomechanics research and clinical applications.