What do you mean my cells are cannibalizing themselves? And it’s happening right now, somewhere in your body, as I type and you read this sentence… However, there is no reason to panic: Autophagy is one of the essential mechanisms that our cells use to keep themselves healthy and viable.

Before explaining a bit about how it works and why it is important, let’s look at the etymology of the word, as @ruth-girl requested in her very creative challenge “It’s all Greek-Science-Geek to me” (I challenge you to say that 5 times in a row, ha!).  Click on the video to have the dubious pleasure of hearing me pronouncing the term in English and Spanish (as I worked with it for a couple of years for my master’s degree back in Mexico, and thus uttered it many, many times) as well as my attempt at pronouncing the Greek words that serve as its root, enjoy!

Thus, the term autophagy means “self-eating”. In short, autophagy is a process that the cells use to degrade cellular components whenever they are old, defective, damaged or excessive for the normal function of the cell.

The material that is about to be degraded is tagged with a “please dispose of” molecular tag, which is recognized by the autophagy machinery. The autophagy machinery recruits lipid membranes that create a membrane enclosing the material that needs to be degraded, hence building a “lipid bag” around it called autophagosome:

Modified from Rodriguez-Rocha, 2011.

Think about autophagosomes as garbage bags that contain the material that will be degraded, which usually consists of old, defective and/or damaged proteins or even entire cellular organelles (like mitochondria); some pathogens can also be encapsulated in this way for degradation. Once this cellular garbage is encapsulated, autophagosomes fuse with lysosomes, which are like the stomach of the cell and contain enzymes that are able to break down and dismantle the organelles, pathogens or proteins into smaller pieces. These pieces (aminoacids, fatty acids) are then recycled and used as building blocks to assemble new molecules or organelles according to the cell’s needs.

Autophagy, thus, has a crucial role in our cells acting as one of the “recycling bins” of the cell (the other one being the proteasome, of which I might talk in another occasion). After its discovery in the 1960’s, many other roles have been discovered for autophagy. 

Did you know?

Last year’s Nobel Prize in Physiology or Medicine was awarded to Dr. Yoshinori Ohsumi, for his discoveries of mechanisms for autophagy.

Thanks to a series of really clever experiments performed in yeast, Dr. Ohsumi was able to determine the most important components that conform the autophagy machinery, as well as getting an insight for understanding exactly how autophagy works – and also very importantly, what happens when autophagy malfunctions. 

What happens when autophagy goes wrong or doesn’t work as it should?

Imagine what would happen when garbage in your city (or in your own home) doesn’t get disposed of and therefore accumulates further and further. Eventually, a point will be reached were your quality of life would be seriously affected. Well, the same thing happens in our cells. Accumulation of damaged, defective or excessive proteins are at the root of neurodegenerative diseases like Alzheimer and Parkinson’s Disease. Also, protein accumulation can cause inflammation or trigger a chain reaction of oxidative damage that can affect healthy proteins and organelles and disrupt their normal function.

To make matters more complicated, under some circumstances, having too much autophagy can also be detrimental. For example, cancer cells are cells that are growing out of control and therefore need a big supply of energy to keep going and proliferating; one of the mechanisms that such cancer cells use to fuel such uncontrolled growth is to degrade cellular materials in bulk in order to obtain energy by “digesting” them.

In other cases, an excess on autophagy induction could lead to the cells digesting past a critical point where they start to degrade cellular components that are still needed for the cell to keep functioning, which eventually can result in cell death.

Therefore, the regulation of autophagy is a very complex, but very promising therapeutic target that opens the possibility to treat some of the most devastating degenerative conditions – be it by restoring the optimal healthy balance, or by manipulating it in such a way that we can use it to get rid of cancer cells.

Benefits of autophagy in your body.

Under normal conditions, autophagy helps our cells to cope with stress, helping them adapt to changing conditions. Also, it is part of the “quality control” of the cell, ensuring that proteins and organelles that have been damaged, are too old or defective are disposed of in a safe manner.

Therefore, it is no surprise that the normal, healthy action of autophagy has restoring and antiaging properties in our bodies. Its normal function also prevents the development of degenerative diseases caused by accumulation of damaged or excessive cellular products.

What are some natural inductors of autophagy?

• Fasting (and also Intermitent fasting), since it is a nutrient-sensitive process that gets activated when there is a scarcity of nutrients in the cell; autophagy takes over to provide the cell with energy and building blocks required for synthesizing new molecules by digesting cellular components that are no longer needed.
• Caffeine is also a known autophagy inducer, as well as other substances like resveratrol (present in the peel of red grapes).
• The stress induced by exercise is also a trigger for the autophagic response, to clear all possible damaged molecules and provide a restorative effect.

Would you like to know more about the effects of autophagy in the human body? The you can take a look at this interview with Dr. Guido Kroemer, one of the world’s lead experts in the field, where he discusses the metabolic impact that autophagy has, as well as its activation during fasting and how it could benefit the body, how autophagy has been shown to slow cellular aging, how it prevents neurodegenerative diseases by clearing away protein aggregates, and also its role in cancer.

You can listen to it while you have your morning coffee!

Until the next time,

Irime  

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References:

•  DNA damage and autophagy.

https://www.ncbi.nlm.nih.gov/pubmed/?term=DNA+damage+and+autophagy+Rodriguez-Rocha

• Nobel Pize Press Release 2016:

https://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/press.html

• Nobel Prize for Autophagy Explains Cell Cannibalism

https://www.inverse.com/article/21681-nobel-prize-medicine-autophagy-cannibalism  

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Image sources: 1, 2, 3, 4, 5