Written by Mary Margarethe R. Cuevas

Edited and Reviewed by Reuben J C. Los Baños, Ph.D.

The lysosome plays a crucial role in cellular survival. It acts as the cell’s garbage disposal system. It also breaks down macromolecules and recycles cellular components. They are always perceived as the degradative organelle of the cell.

We all know that cells are the basic building blocks of life. They are the smallest units of life. But, they also carry out all the functions needed to keep organisms alive. Inside the cell, it has even smaller parts that we call as organelles. These organelles all perform different functions for our cells to operate.

One organelle that we all know is the nucleus. It is the one that stores all our genetic information. But, there is also this one tiny organelle that will be the subject in this article. Scientists call it the garbage disposal system of the cell, but it does much more than that.

Recent studies realized that lysosomes take part in other cellular processes. They are also involved in the killing of cellular pathogens. These pathogens are organisms that can grow and reproduce inside a host. Lysosomes are also involved in lysosomal membrane repair.

Damaged lysosomal membrane leads to cytoplasm leakage. When this happens, it needs to be immediately repaired. But, if a cell becomes damaged beyond repair, it will undergo cell death. It repairs itself through self-death, or apoptosis. This mechanism is crucial to not harm the surrounding cells. The lysosome is responsible for this job.

These are only some of the important cell processes that involve the lysosomes. Without them to perform these functions, the effects to our body can be detrimental.

What is the role of lysosomes in health and disease?

Lysosomes play a vital role both in health and disease as the cell’s disposal and recycling system. All the time, we are ingesting bacteria. Yet, we don’t always get sick or infected. Though there may be good bacteria, there are bad ones as well.

One of the many things that kept us healthy from bacterial infections are the lysosomes. Cells will ingest the bacteria and send it into its lysosome for destruction. As of now, we all know about the breakdown and recycling function of lysosome. They are able to do this due to the enzymes present in it.

These enzymes, known as hydrolytic enzymes, break down large molecules into small molecules. Our body needs to break large molecules into smaller molecules to use it. If this breakdown does not occur, it can result in a Lysosomal Storage Disease. This causes the lysosome to lose its function and the “trash” inside it accumulates.

Small molecules can turn to large molecules. This also happens inside the lysosomes. Yet, sometimes they can’t get out of it because the transporters needed for it are missing. Additionally, lysosome functions as sensors. They can tell if a cell is healthy or not or if it is being attacked, and track energy levels.

What is the role of lysosomes in cell death?

When damage occurs to a cell, it undergoes a mechanism called apoptosis. This mechanism is done by the lysosome. It is a crucial step to remove unnecessary and broken cells. These cells may hinder an organism’s growth and development when not removed. What happens is that our cells will receive signals to undergo apoptosis.

The lysosomes will then release their enzymes to the cytosol. Its lysosomal membrane breaks down, allowing the release of cathepsins and other proteases. These released enzymes activate a series of events that will end up killing the cell. We call this process Lysosomal Membrane Permeabilization (LMP).

Moreover, lysosomes are also involved in other forms of regulated cell death. The extent of lysosomal damage determines the type of cell death occurring. If a cell experiences partial damage, it still may undergo apoptosis. Some cells though undergo complete rupture. This results in what we call Necrosis.

How do lysosomes protect themselves from getting degraded by the enzymes present inside them?

We now know that lysosomes contain enzymes with digestive and hydrolytic functions. This time, are we not curious as to how the lysosomes protect themselves from degrading? Lysosomes are able to protect themselves through several mechanisms:

• Membrane protection – The lysosomal membrane itself serves as a protective barrier. A lipid bilayer composes the membrane and can withstand an acidic environment. Inside the lysosome is acidic due to the enzymes inside it. This gives the membrane another function. It keeps on these enzymes inside the membrane.

• Acidic environment – The lysosomal enzymes are also known as acid hydrolases. The acidic conditions inside the lysosome (pH 4.5 – 5.0)  is what activates the enzymes. The cytosol on the other hand is in neutral pH (pH 7.2) which can inactivate the enzymes when released outside.

• Repair mechanisms – When a damage manifests to the lysosomal membrane, the cell can start repairing it. This mechanism will restore the membrane’s integrity and prevent enzyme leakage. The cell does this by recruiting proteins that can help patch or repair any damage.

Can humans survive without lysosomes?

You have now reached this part of the article. By this time, we should have a similar response to this question. Indeed, humans cannot survive without lysosomes. We learned that the lysosome plays a role in important cellular processes.

As the cell’s disposal and recycling system, they facilitate autophagy and endocytosis. Basically, it digests internal and external materials. Examples of these are degrading proteins into amino acids and carbohydrates into simple sugars.

We also discussed how lysosomes play a role in the immune response. It is the one who destroys the invading bacteria and viruses to your body. Phagocytic cells engulf pathogens and enclose them in phagosomes through autophagy. Fused with lysosomes, they form phagolysosomes and then degradation occurs.

Cases where cells can be damaged beyond repair is possible. When this happens, the damaged cell can affect other cells. To avoid this from happening, the cell resorts to initiating self-death. This is done by the lysosomes by releasing their enzymes that break down the cellular components.

What happens when a lysosome dies?

It is now a familiar knowledge that lysosomes face death. Now, we start to wonder what actually happens after they die. Some of it was already discussed in this article. But what happens next? Will they disappear? Do they lie around the cytosol? Can they restore back as lysosomes? We will start answering these questions one at a time.

• Lysosomal membrane permeabilization – What happens first when lysosomes die is their membrane permeabilizes. The enzymatic contents inside such cathepsins will leak into the cytosol.

• Release of hydrolytic enzymes – The released enzymes from the lysosome will begin a series of reactions that will lead to the cell’s death. These reactions can also activate apoptotic pathways that promote apoptosis or necrosis.

•  Cell death pathways – We must know that there are different types of cell death. The type varies depending on the amount of lysosomal leakage. Cell death can be through apoptosis or necrosis. When we say an apoptotic death, the leakage is more regulated. Moreover, necrotic death has extensive and uncontrolled leakage.

• Effect on cellular homeostasis – We learned that the lysosome lumen is acidic. This is due to the hydrolytic enzyme inside it that is active at acidic pH. Once the cytosol receives all these, it may trigger inflammatory responses. These responses  will then contribute to more damage to its surrounding cells.

• Potential recovery – Our cells have mechanisms to recover from moderate LMP. It is through a process called lysophagy. The damaged lysosomes are removed through autophagy. This helps restore cellular function and maintain homeostasis. Note that this can only happen if the damage is not severe.

What is the role of lysosomes in aging?

We will now dive into the last part of this discussion. What does lysosomes have to do with aging?

A scientist in the name of Meng Wang tried to study the secrets tolongevity. Living in a family where longevity seems to run in their blood, she was curious. Wang, together with her team, discovered anti-aging signals in roundworms. These signals came from the lysosome.

In the study, the team discovered that lysosomes trigger a chain reaction of messages. This happens when the lysosome produces a specific fatty acid called dihomo-gamma-linoleic acid. These reactions are then what causes the roundworm’s life span to prolong.

Worms only live for 20 to 25 days. But in their study, the worm’s lifespan increased by 17 days. Additionally, the anti-aging signal that caused this longevity came from a fat tissue. Yet, it was still detected by neurons and tissues elsewhere in the worm.

This study opened doors for other scientists. They wanted to learn more about the other functions the lysosome may have. As for Wang, she didn’t stop there. She believes that there’s still more to discover.

More about it

Just like Meng Wang, there are other scientists out there studying the lysosome. One example would be the study of Shou Wang and her colleagues from Baylor College of Medicine. In the study, they investigated the role of lysosomes in brain function and Alzheimer’s disease.

There is another study from the Tokai National Higher Education and Research System. It is the link between lysosomal and their focal adhesion to cancer cells. Research on cancer treatments has already started a long time ago. The possibility for lysosome as a new therapeutic treatment for cancer contributes to its medical relevance.

Conclusion

Despite their size, lysosomes proved themselves to be important. As I like to appreciate the role of lysosomes, I think of this analogy. Our cell is like a community and lysosomes are the garbage collectors. The garbage collectors only had one main job to do in our community.

But, what we fail to realize are the results of their work. They keep our community clean. We are also far from the risks of diseases. Trashes can contribute to floods if not thrown properly. Instead, they are reused and recycled to other materials. This is exactly what lysosomes do.

Lysosomes protect us from pathogens that cause diseases. They clean our cells by collecting the unused materials in it. Recycling them to materials that can be used by our body. Moreover, it monitors our energy levels. It maintains the cell’s health and responds to stress.

I hope that this article shows you how fascinating it is that we learn more about our body. The more that we learn about it, the more we get to appreciate all of its parts, even the tiny ones.

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