Living cells are like miniature factories, responsible for the production of more than 25,000 different proteins with very specific 3-D shapes. And just as an overwhelmed assembly line can begin making mistakes, a stressed cell can end up producing misshapen proteins that are unfolded or misfolded. Now Duke University researchers in North Carolina and Singapore have shown that the cell recognizes the buildup of these misfolded proteins and responds by reshuffling its workload, much like a stressed out employee might temporarily move papers from an overflowing inbox into a junk drawer.

The study, which appears Sept. 11, 2014 in Cell, could lend insight into diseases that result from misfolded proteins piling up, such as Alzheimer's disease, ALS, Huntington's disease, Parkinson's disease, and type 2 diabetes.

"We have identified an entirely new mechanism for how the cell responds to stress," said Christopher V. Nicchitta, Ph.D., a professor of cell biology at Duke University School of Medicine. "Essentially, the cell remodels the organization of its protein production machinery in order to compartmentalize the tasks at hand."

The general architecture and workflow of these cellular factories has been understood for decades. First, DNA's master blueprint, which is locked tightly in the nucleus of each cell, is transcribed into messenger RNA or mRNA. Then this working copy travels to the ribosomes standing on the surface of a larger accordion-shaped structure called the endoplasmic reticulum (ER). The ribosomes on the ER are tiny assembly lines that translate the mRNAs into proteins.

When a cell gets stressed, either by overheating or starvation, its proteins no longer fold properly. These unfolded proteins can set off an alarm -- called the unfolded protein response or UPR -- to slow down the assembly line and clean up the improperly folded products. Nicchitta wondered if the stress response might also employ other tactics to deal with the problem.