Klionsky lab identifies new proteins required for autophagy
July, 2011 – Life Sciences Institute professor Dan Klionsky and colleagues have found that SNARE proteins, a class of proteins previously known for assisting with other vesicle fusion events in the cell, play a role in forming the autophagosome, which is a key step in autophagy. They published their results in the July 22 issue of the journal Cell, along with five other labs from around the world who collaborated on the discovery.
Autophagy is a cellular pathway involved in the disposal of excess or defective proteins and organelles. Although there are positive effects of autophagy, such as protecting the cell and removing unneeded or defective debris, autophagy malfunction is linked to cancer, neurodegeneration, microbial infection, and aging.
“With this work we were asking how the autophagosome forms—it’s a critical part of autophagy and the autophagosome is a dynamic structure since it can be many different sizes,” says Klionsky, who is also professor of Molecular, Cellular and Developmental Biology with the College of LS&A.
Klionsky’s recent work reports that it is SNARE proteins, rather than the ubiquitin-like protein Atg8as previously published, that are involved in the fusion steps needed for development of the complete autophagosome structure. This insight is the result of a collaboration between Klionsky’s lab, which specializes in yeast studies, and five other labs who contributed expertise in yeast, mammalian systems, and electron microscopy. The other labs are located at Yale University, Memorial Sloan Kettering Cancer Center, Rice University, University Medical Centre Utrecht in The Netherlands and Kogakuin University in Tokyo, Japan.
Their findings are featured on the cover of the July 22, 2011 issue of Cell.
Understanding the complex process of autophagy is important since it is known to have association with deadly diseases. “We are interested in being able to precisely control the process—either shutting it off or turning it on,” Klionsky says, “As we identify more players and uncover more details it will give rise to finding ways of regulating autophagy.”
This work was supported by grants from the National Institutes of Health, the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research.