Our long-term goal is to decipher dynamic changes and the physiological significance of communication among organelles in disease onset. While organelles are compartmentalized and function independently in the cell, organelles communicate with each other to maintain cellular homeostasis. We previously demonstrated that the oncogenic mTORC1 signaling pathway controls mitochondrial dynamics and activity by selectively promoting the translation of nucleus-encoded mitochondria-related mRNAs, which engenders an increase in ATP production, a required energy source of mRNA translation in cancer cells. This finding suggested that the mTORC1 pathway is involved in the formation of mitochondria-riboso...

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Our long-term goal is to decipher dynamic changes and the physiological significance of communication among organelles in disease onset. While organelles are compartmentalized and function independently in the cell, organelles communicate with each other to maintain cellular homeostasis. We previously demonstrated that the oncogenic mTORC1 signaling pathway controls mitochondrial dynamics and activity by selectively promoting the translation of nucleus-encoded mitochondria-related mRNAs, which engenders an increase in ATP production, a required energy source of mRNA translation in cancer cells. This finding suggested that the mTORC1 pathway is involved in the formation of mitochondria-ribosomes communication in tumors.

To study alternations in organelle contacts during tumorigenesis, we generated an obesity-induced HCC model in which mTORC1 is aberrantly activated by oncogenic and nutrients signals. Our preliminary transparent electron microscopy (TEM) analysis discovered the formation of mitochondria-ribosome-ER contact during the development of obesity-induced cancer and observed enlarged ER around fragmented mitochondria and numerous ribosomes between mitochondria and ER only in tumors.

These results led us to conceive a substantiate groundbreaking concept that ribosomes mediate communication between mitochondria and ER to utilize energy efficiently and drive protein synthesis that leads to ER stress. To test our hypothesis, we will employ multidisciplinary approaches, including a series of genetically engineered mice, TEM analysis, and omics technologies in mice and human samples. Successful completion of this proposal will provide an innovative concept that organelle communication maintains energy and protein homeostasis and lead to new preventive and therapeutic strategies that will reduce the toll of obesity-induced liver cancer.

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