New insights into how cells transport their waste for recycling



Scientists at Sanford Burnham Prebys have better understood the intricacies of autophagy, the process by which cells break down and recycle cellular components. The conclusions, published in Current biology, describe how the “garbage bags” in a cell – called autophagosomes – are labeled to direct their movement to cellular “recycling factories” where the wastes are processed. The research opens new avenues for understanding the relationship between autophagy and age-related diseases such as cancer and neurological disorders.

“Our latest study identifies how a chemical change (phosphate-linked tag) of a key component of the autophagosome, the protein called LCB3, helps direct the transport of autophagosomes into the cell in the right direction,” explains Malene Hansen, Ph.D., professor at Sanford Burnham Prebys and lead author of the study. “We previously reported that LCB3, which is found on the surface of autophagosomes, must be labeled for autophagy to work effectively. We now have a better understanding of how labeling occurs and its importance for autophagosome movement.”

In addition to their own lab studies, the Hansen lab has worked with colleagues in the lab of Sandra Encalada, Ph.D., at the Scripps Research Institute in San Diego, leaders in the transport of cellular components into neurons. These investigations showed that blocking the chemical modification of the LC3B protein disrupted the efficient transport of autophagosomes to plants for cell recycling.

“Transporting waste in a cell is like moving garbage trucks on a highway,” says Jose Luis Nieto-Torres, Ph.D., post-doctoral fellow at the Hansen Laboratory and first author of the study. “With our collaborators, we studied the process in nerve cells because they are long and flat, which helps us to observe the directional aspects of transport, a critical aspect for recycling waste via autophagy.

“We clearly saw that if the phosphate labeling of LC3B was hampered, the autophagosomes or the trash bags filled with waste did not make their way to the lysosomes – the cell recycling plant. This is potentially very harmful to the health of a cell. It’s somewhat analogous to what would happen if a garbage truck didn’t pick up your trash – your trash could accumulate, scatter around the neighborhood and create a health hazard. “

As a next step, the researchers want to determine which waste is selected for recycling and how a cell determines when to start moving the waste.

“My lab’s research efforts focus on the relationship between aging and autophagy,” concludes Hansen. “Based on this discovery, we have a potential new entry point to modulate recycling activity in a cell, which may be relevant for understanding the decreased functions of autophagy that are known to occur. in aging cells. Such information could ultimately lead to new drug targets to fight age-related diseases as well as potential diagnostic markers to assess the “health” of autophagy, an important goal for the future. “

Reference: Nieto-Torres JL, Shanahan SL, Chassefeyre R, et al. The phosphorylation of LC3B regulates the binding of FYCO1 and the directional transport of autophagosomes. Curr Biol. 2021: S0960982221007508. do I: 10.1016 / j.cub.2021.05.052

This article was republished from the following materials. Note: The material may have been modified for its length and content. For more information, please contact the cited source.


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