Author: Sara Wong
Editors: Sarah Kearns, Ellyn Schinke, and Shweta Ramdas
Taking out the trash is a despised chore. It’s smelly and heavy, and you have to get off the comfortable couch, put on shoes, and take it all the way to the curb. Yet, we do it because we understand that it is important for the health of our homes and neighborhood, and taking out the trash is better than leaving it in the house.
What you might not realize is that your cells also have to take out the trash. In fact, defects in this process often lead to disease. One example is Niemann-Pick disease, which in severe cases causes death in early childhood. Neimann-Pick disease is caused by defective lysosomes, the trash bins of the cell. In order to understand diseases like Niemann-Pick disease, we must first understand lysosomes.
Lysosomes: Cell’s Sanitation System
In the same way that towns and cities have sanitation systems to handle our daily debris, the cells of your body also have ways to handle their own trash. These unwanted materials include damaged cellular compartments, protein aggregates, and viruses. Cells have several pathways for handling waste, but most of them involve the lysosome. Lysosomes are small acidic sacs that contain enzymes that break down unwanted materials. Lysosomes are analogous to sanitation systems.
The waste first needs to get to lysosomes to be processed. Cellular waste can be targeted to lysosomes using tethers, like docking stations for garbage trucks. In a sanitation system, trucks from all over the city bring trash to the garbage plant where they dock and unload the trash. The plant then processes and breaks down the trash. Some of it will end up in a landfill, while some might get recycled. In our cells, once waste is inside the lysosome, the enzymes break it up. The lysosome will then export some of the trash out of the cell, while sending some materials to other parts of the cell to get recycled.
For the lysosomal enzymes to work, the inside of the lysosome must be much more acidic than the rest of the cell. It’s as if a garbage compactor could only work in a tank of lemonade. To make the inside of the lysosome acidic, specialized pumps selectively bring acidic particles into the lysosome.
When Lysosomes Can’t Process Cellular Waste
From receiving waste to processing it, waste management is mostly invisible and usually taken for granted. Sanitation is one of those things that you don’t truly appreciate until it’s gone: when a sanitation department goes on strike, the city notices within days. Trash piles up quickly, physically blocking traffic and causing the streets to smell. As a result, these strikes are usually resolved quickly—since the machinery is not broken, operations soon return to normal.
However, when the sanitation system fails in your cells, it’s more often because the essential machinery is damaged, not because the lysosomes “go on strike.” Problems can arise at any step – docking to the lysosome, generating the enzymes inside, or keeping the lysosome acidic. Unlike sanitation strikes, where the machines can be turned back on at any moment, these problems in the cell cannot be resolved at the flip of a switch. Instead, the cell desperately tries to turn on the machinery while the trash piles up. This can lead to fatal diseases.
Several diseases have been linked to defective lysosomes. One group of genetic diseases known as lysosomal storage diseases vary in their symptoms, which include neurological disorders, heart problems, and abnormally sized organs and bones. In these diseases, the cellular waste piles up in the cell. Similarly to how piles of garbage in the streets cause traffic jams, the accumulated cellular waste prevents other cell functions from proceeding efficiently. In Niemann-Pick disease, lysosomes cannot recycle fat as efficiently, causing fat to accumulate in the body and kill cells—ultimately causing damage to many organs.
Currently, there are no cures for lysosomal storage diseases, and treatments are largely experimental. They attempt to address one or both sides of the problem, by limiting the cellular waste and/or rebuilding the damaged lysosomes. To limit cellular waste, some drugs try to prevent the production of the waste product – if you can’t take the trash away, try to make less of it. To rebuild damaged lysosomes, therapeutics either replace or enhance the lysosomal machinery. Damaged lysosomal enzymes may be replaced through bone marrow transplants or introduced to the body by IV. To enhance lysosomal activity, the patient may take drugs that increase enzyme activity – if fewer garbage plants in your cell are working, then have them work faster.
Some drugs are still in clinical trials or have only been recently used in patients, and it is largely unknown how these drugs specifically affect lysosomes. Unfortunately, most of these therapies do not address neurological problems, some of the most serious symptoms of lysosomal storage diseases. In order to improve the treatments, researchers need to further investigate how lysosomes work. We understand that lysosomes are the sanitation system, but how do their smaller departments work? With a better understanding of how cells clear waste, we may develop better treatments for related diseases that address all the symptoms associated with a defective sanitation system.
And the next time you complain about taking out the trash, remember how your very own cellular disposal system works day and night to keep your body healthy.
About the author
Sara is a doctoral student at the University of Michigan in the Cell and Molecular Biology Program. She studies how the cell delivers cargoes to the correct place at the correct time. Sara was born and raised in New York City where she earned a BA in Biology from Macaulay Honors College at Queens College. Outside of lab, she enjoys running, painting, rock climbing, cooking, and petting her friends’ dogs.
Read all posts by Sara here.