Biological complexity: actions of lysosomes (Introduction)

by David Turell , Wednesday, October 25, 2023, 22:26 (184 days ago) @ David Turell

Newly developed methods of study:

https://phys.org/news/2023-10-lysosomes-quick-

"The researchers were able to show for the first time that lysosomes undergo a massive transformation. A signaling lipid acts as a switch between the two states.

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"Nutrient availability in the body is constantly changing. For example, after a full meal, cells have many more nutrients available than at the end of a long night without any food intake. "It is important for all cells and tissues to be able to respond to the current food intake in such a way that certain basic building blocks are always present inside the cell," explained Professor Volker Haucke,

"These basic building blocks are obtained through catabolism, the process by which ingested nutrients are broken down into small components that the cell uses to make the molecules it needs.

"One of the components responsible for this is the lysosome, a membrane-enclosed sac. At the same time, lysosomes are the central monitoring point that determines whether the food supply in the cell is good or bad. When there is a good supply of nutrients, the mTOR signaling pathway on lysosomes is activated, inducing cell division and growth. When nutrients are scarce, the mTOR complex is switched off to stimulate catabolic programs. As a result, lysosomes combine two opposing tasks: degradation and assembly.

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"In a complex cascade, this process is controlled by signaling lipid molecules that induce either a starved or a fed state. Using correlative light and electron microscopy, the researchers observed that there are two pools of lysosomes in the cell: Small motile ones, located more at the periphery, act as monitoring stations.

"Meanwhile, larger, more static lysosomes, located closer to the nucleus, are responsible for degradation. What changes is the ratio: In a well-fed state, the small motile lysosomes carrying the active mTOR complex predominate, and there are relatively few static lysosomes. When the cell starves, the small motile lysosomes lose the signaling lipid marker for mTOR and acquire a new signaling lipid, activating the digestive enzymes in the lysosome.

"This response is acute, meaning that the cells are transformed immediately, and initial changes can be observed within minutes. The process from destructive to constructive metabolism is completed in one to two hours," reported Michael Ebner.

"The signaling lipids act as a switch that activates or switches off the mTOR complex, depending on nutrient availability. "Lysosome properties change completely, depending on the signaling lipid," emphasized Volker Haucke. This makes the new findings interesting for therapeutic purposes. After all, during active degradation, lysosomes also remove damaged proteins. And if you can flip the signaling lipid switch artificially, you can also influence the metabolic events in the cell."

Comment: Another example of an irreducibly complex set of on/off controls which can only be developed by design.