When two people strike up a friendship, sometimes their spouses, children or even pets become friends too. In the case of Dr. Ami Navon
and Prof. Zvulun Elazar
, biologists and friends at the Weizmann Institute, their comradeship extends to the molecular pathways they study. They have recently discovered that two of them collaborate in case of need.
Navon studies the proteasome, the cell’s major “garbage disposal” system: This molecular complex destroys and recycles defective proteins – for example, ones that are not folded properly and therefore cannot perform their function in the body. Elazar investigates the lysosome, another recycling machine. The lysosome also carries out destructive tasks, but not as selectively as the proteasome: If a cell turns cancerous, the lysosome might destroy cellular compartments “in bulk” in order to induce the cell to commit suicide.
Navon decided to find out: Do these two destructive mechanisms interact? Answering this question is important because improper breakdown of proteins can be catastrophic for human health. For instance, faulty recycling of certain proteins might cause cystic fibrosis or such neurodegenerative diseases as Parkinson’s or amyotrophic lateral sclerosis; on the other hand, excessive recycling is typical of multiple myeloma and autoimmune disorders.
To explore the relationship between the proteasome and the lysosome, Navon and postdoctoral fellow Dr. Edith Kario, both of the Biological Regulation Department, teamed up with the Biological Chemistry Department’s Elazar and postdoctoral fellow Dr. Nira Amar. Their study results
, reported in the Journal of Biological Chemistry
, show that the proteasome and the lysosome can indeed lend each other a helping hand when necessary. When the proteasome fails to destroy a target protein, causing this protein to accumulate in the cell, the lysosome springs into action. Working with yeast, the scientists have revealed how this happens: A cellular process called autophagy attaches a “label” to the accumulated protein, thereby signaling to the lysosome that its help is needed; the molecular elements of autophagy then “escort” the accumulated protein to the lysosome, which destroys it effectively. Thus, when the main protein recycling machinery is out of order, a secondary recycling complex takes over.
These findings might in the future help in the development of new approaches for treating diseases involving faulty protein breakdown. In those tied to proteasome malfunction, for example, its activity might be enhanced with the help of the lysosome – just the kind of help one would expect from a good friend.
Prof. Zvulun Elazar’s research is supported by the Louis Brause Philanthropic Fund; and the Yeda-Sela Center for Basic Research. Prof. Elazar is the incumbent of the Harold L. Korda Professorial Chair of Biology.
Dr. Ami Navon is the incumbent of the Recanati Career Development Chair of Cancer Research in Perpetuity.