STING Protein Helps Clear Cellular Stress in Addition to Known Role in Inflammation

A new study published in Molecular Cell has revealed that the protein STING, known for its role in inflammation, also plays a crucial part in cellular stress management. This discovery, led by researchers at the University of Pittsburgh, sheds light on STING's unexpected protective function  and could have implications for future development of therapeutics for age-related diseases.

To learn more about potential benefits of STING activation in response to diverse stresses, senior author Jay Xiaojun Tan and his team analyzed the full set of proteins within cells. They found that when STING was activated, two transcription factors called TFEB and TFE3 were shuttled to the nucleus of cells, where they activated genes that resulted in the production of more lysosomes. 

“Lysosomes are organelles that are involved in autophagy, a cellular process that cleans up damaged material, almost like a housekeeping or recycling system,” said Tan. “In response to STING activation, cells used TFEB and TFE3 to produce more lysosomes and increase autophagy.” 

Both lysosomes and autophagy are tightly linked with longevity and healthspan, suggesting that this protective function of STING is important for healthy aging.  

STING-blocking therapies are currently being explored within the context of age-related diseases, but according to Tan, the new findings suggest that this strategy should be reconsidered because it would also block the autophagy/lysosome-promoting functions of STING. Instead, selectively targeting components of the inflammation pathway downstream of STING may be a better approach because it would preserve the protein’s beneficial functions.