When cells are deprived of nutrients, they enter a state of stress called autophagy, in which they break down their own proteins and organelles to recycle the components. This process is essential for cell survival, but it can also be harmful if it is not properly regulated. In some cases, autophagy can lead to cell death.
The researchers found that starving cells hijack protein transport stations called translocons to import nutrients. Translocons are normally used to transport proteins into the endoplasmic reticulum (ER), a cellular compartment where proteins are folded and modified. However, when cells are starving, they reconfigure translocons to import nutrients instead.
This reconfiguration is made possible by a protein called ATF4, which is activated in response to starvation. ATF4 binds to the translocons and changes their structure, allowing them to import nutrients.
The researchers also found that ATF4 levels are elevated in cancer cells, which suggests that this pathway could be a target for cancer therapy. By inhibiting ATF4, it may be possible to prevent cancer cells from hijacking translocons and importing nutrients, leading to cell death.
"This study provides a detailed understanding of how starving cells hijack protein transport stations to import nutrients," said senior author Professor Jennifer Doudna, a biochemist at Berkeley. "This could lead to new therapies for treating cancer and other diseases that involve rapid cell growth."
The research team is now investigating the role of ATF4 in other cellular processes, such as protein folding and degradation. They also plan to study how ATF4 levels are regulated in cancer cells.
