Autophagy: Processes, Impact & Function

8 min readDec 31, 2020

There are 30,000,000,000,000 cells in our bodies. About 50–70 billion per day are created. But the truth is, there are a lot of mistakes our body makes. Here comes the cell eater, and live saver autophagy

In this article we talk about:

The Autophagic Process
The possible upsides of autophagy
The risks associated with Autophagy.
The problems with autophagic defects.

A Quick Intro

Autophagy is the body’s cellular process in which the body degrades cellular matter, mainly in the cytoplasm, both randomly and targeted, in order to create amino acids for the body, which we use as energy. In basis, it’s the bodies way of eating its own cells for energy. It has been found to be kickstarted by intermittent fasting, though this claim is still debated. Japanese cell biologist Yoshinori Ohsumi won the Nobel Prize in Medicine in 2016 for his research on autophagy, of which there was proof of marginal longevity and positive impact on cell renewal.

Process

The autophagic process is lengthy, and contains multiple steps in order to discard organelles and unneeded proteins from the cytoplasm

1. Induction

Autophagy is usually triggered by nutrient starvation, but lack of other factors such as carbon, auxotrophic amino acids, nucleic acid have all been found to trigger the process.

Even though there are many reasons of which autophagy is triggered, it is still unknown how the cells sense depletion of these factors. A possible sensor for this process is GCN2, which has been shown to stimulate amino acid signals to the nucleus. But, in a multi cellular organism like humans, each cell does not need to sense nutrient availability or any other factor deficiency, and rather most scientists believe that autophagy is regulated by the organism’s own system, such as the immune response, or the endocrine system, due to their organization of cell responses.

Overall, the induction of autophagy is varied by multiple factors within the body. Really, autophagy is kickstarted by deficiencies of the basic needs of the cell, but the way that the cell senses these deficiencies is still debated.

2. Formation of the Autophagosome.

The next step of autophagy is to target a specific part of the cell, and start the process.

Organelles and proteins in the cytoplasm are isolated, by the phagophore (isolation membrane). As the phagophore isolates the organelle, it elongates, and begins to form around it. This elongation of the phagophore results in the creation of an autophagosome, a double membraned organelle. This where autophagy will later occur, but in the current stage, the autophagosome is just keeping the organelle inside it, not degrading it or even really doing anything to it.

Ap- Atg proteins are the proteins that have been credited to the formation of the autophagosome. They are essential for the formation of the membrane, and the function of these proteins has been extensively reviewed.(Klionsky et al. 2003; Kabeya et al. 2007)

It’s been found that autophagosome membranes cannot recognize what they enclose, and therefore it’s been found that these isolations, and sequestration of organelles within cell, is mainly random. But, some autophagosome membranes can recognize proteins and organelles by their surfaces.

3. Degradation

The next step of the autophagic process, is the degradation of the organelles and proteins that have been trapped inside the autophagosome. This starts with autophagosomes fusing with lysosomes, (which are cells that contain enzymes for degradation). Once bonded with the lysosomes, enzymes are released into the autophagosome for degradation, in which the organelles, and proteins are broken down. This step is the most important part of the process, but is the least known about, as it is difficult to measure the degradation, while inside the autophagosome.

The degrading structures are often called autolysosome, and are continuously being broken down by lysosomes which are receiving continuous flow from the endolytic path.

Function

Amino Acid Use

Necessary amino acids are produced in autophagy, and once the process of autophagy is over, the amino acids are used.

While it’s not completely understood how these amino acids that re generated are used, there are 3 main pathways that these acids go.

Carbohydrate storage

After bouts of starvation, the carbohydrate storages in your bodies are used. After this, glucose is supplied to the liver in order to stay active. Lactates and amino acids have been found to be used in this process, and autophagy may be a big contributor to this process.

Energy Source

Amino acids have also been found to be used as an energy source through the TCA (tricarboxylic acid cycle). It has also been found that amino acids are important in homeostasis, and cell proliferation.

Protein Synthesization

Protein synthesis is initiated universally with the amino acid methionine. In E-coli, studies with sequence mutants of the initiator methionine tRNA have shown that protein synthesis can be initiated with several other amino acids.

Overall, cell survival depends on the amino acids produced by autophagy, especially under conditions such as metabolic stress.

Damaged Protein Removal

Many recent studies have shown that autophagy is a key component in managing protein and organelle quality within the cytoplasm. This was proven, by when a study found an abnormal amount of proteins or organelles in autophagy deficient cells, and even in disease related mutant protein.

Some types of autophagy’s main aim is to get rid of needed organelles. An example of this is when damaged mitochondria are seemingly targeted and eliminated by autophagy.

Overall, this part of autophagy has piqued the interest of many researchers, due to its applications in the field of longevity, and cell based disease prevention.

What Does This Mean?

Autophagy has the potential to solve major problems in disease care, and already is doing so

Here are some major things scientists are attributing autophagy:

Removing toxic proteins from the cells that are attributed to neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease
Recycling residual proteins
Providing energy and building blocks for cells that could still benefit from repair
On a larger scale, it prompts regeneration and healthy cells

Here are some diseases we believe it prevents:

Wilson’s disease
Acute liver injury
Nonalcoholic fatty liver disease
Chronic alcohol-related liver disease

Autophagy is receiving a lot of attention for the role it may play in preventing or treating cancer, too.

Autophagy also seems to play an essential role in the immune system by cleaning out toxins and infectious agents.

There is also evidence that autophagy may improve the outlook for cells with infectious and neurodegenerative diseases by controlling inflammation.

The possible risks

Autophagy is beginning to seem like a miracle cure, but as scientists begin to uncover more and more on this topic, risks have begun to become more apparent.

Random Elimination

Many scientists believe that autophagy is a random process, of which the autophagosome is only triggered by nutrient starvation, and degrades whatever matter within the cytoplasm it can find. If autophagy randomly degrades organelles within the cell, many healthy cells may become less productive, due to lack of enough good proteins and organelles.

Cell death

When autophagy specifically targets mitochondria by selective autophagy, the cell loses its energy source. Many times this leads to cell death due to lack of energy within the cell. At the same time, extensive autophagy is commonly observed in dying cells, leading to its classification as an alternative form of programmed cell death. Though sometimes autophagy based cell death is good in cells that lack apoptosis, autophagy cell death in healthy cells is incredibly bad.

Autophagy Defects

Autophagy also can do some pretty bad stuff if it doesn’t work right.

Neurodegenerative diseases

When autophagy has defects within it’s process, there are also very dire results. An accumulation of autophagic vacuoles has been found in many neurodegenerative disease such as Parkinsons and Alzeihmers. While scientists aren’t sure exactly if the reason for the accumulation of vacuoles was due to an unusually high amount of autophagic production, or some sort of disruption of the process. What’s known is that mutant cells and proteins degradation is very important and largely attributed to autophagy, and when it doesn’t do its job, bad things happen.

Tumors

Another outcome from defects in the autophagy process is the growth of tumors. The reason for this is, many reports suggest that autophagy is a tumor suppressor. When autophagy malfunctions, its tumor suppressors no longer functions and the tumor grows. It was also found that loss of autophagy causes cell death, which may help tumors due to an inflammatory response.

Conclusion

Autopathy gives us an interesting insight of how the body tries to keep humans living longer, and without major cell based mutation diseases. But as outside factors such as pollution and radiation begin to affect us on a cellular level, many people have begun to ask, which is natural autophagy enough?

If we are in an age of cell danger, should we be trying to make our natural cell guard better?

Induction will still have to be more researched, as we still are trying to figure out the exact formation of inductions, and the true risks of a process like this. Autophagy induction will continue to grow as an industry and science, but is it really worth it? To be honest… who knows? Autophagy symbolizes the beauty of the human body, the fact that nature even took into consideration that our cells had flaws. But obviously it hasn’t been enough to make us live forever. Autophagy is still a science in its infancy, a process that still seems very promising, but still very unresearched and unknown.

But, autophagy research really symbolizes the jumps scientists have been making in order to finally understand the human body, and the true complexities of the bodies cellular process, and more than that, its awareness of the flaws it contains, and the true adaptation of weeding out the reasons we die at the cellular. Autophagy. The self eating, life saving, maybe tumor causing, cellular superhero.

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