<figcaption> Credit: © Professors Pietro M. Motta & Tomonori Naguro / Photo Researchers, Inc.</figcaption>
Credit: © Professors Pietro M. Motta & Tomonori Naguro / Photo Researchers, Inc.

The paper:

T. Yorimitsu et al., "Endoplasmic reticulum stress triggers autophagy," J Bio Chem, 281:30299-304, 2006. (Cited in 48 papers)

The finding:

University of Michigan biologist Daniel Klionsky and a group of researchers wanted to see if stressing a yeast cell organelle would initiate autophagy - a degradation process cells use to clear misfolded proteins. Klionsky and his colleagues stressed the endoplasmic reticulum (ER) by disrupting protein folding with chemicals. In doing so the researchers triggered autophagy to clear the misfolded proteins and restore normal ER function.

The synchronicity:

Around the time this Hot Paper appeared, other groups demonstrated ER stress-inducing autophagy in mammalian cell lines, and went further to identify the mechanisms that translate ER stress to the induction of autophagy.

The mechanism:

Since Klionsky's paper, says Xiao-Ming Yin, an experimental pathologist at the University...

The future:

Yin's group is exploring how to improve cancer therapy by using one drug to induce ER stress while another inhibits autophagy in tumor cells. This seriously disrupts crucial processes in tumor cells and leaves them with compromised defenses because their degradation processes are impaired. "We can show in cell culture," says Yin, "that we can enhance the killing [of tumor cells]."

Autophagic Response to Chemical ER Stressors
Chemical % Yeast Cells Showing Autophagy
Dithiothreitol (DDT) 50
Tunicamycin (TM) 46
No treatment 19

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