2023-05-17 09:29:46
By Laura Baños Carrion* (CSIC)
From the time we get up to the time we go to bed, human beings constantly generate garbage. Getting rid of it is a simple and daily act, and we find a container where we can throw it away a few steps from our homes and jobs. Our cells also make junk all the time, but how do they get rid of it? The mechanism they use to stay clean is known as autophagya term that comes from the Greek y which means “to eat oneself”.
Autophagy is the way cells maintain themselves in optimal and healthy conditions, avoiding the accumulation of waste products that could affect their functionality. It is a cleaning system by which, as if they were a vacuum cleaner, the cells swallow the dirt, which in their case would be all those cellular components and damaged proteins, which do not work properly or that they simply no longer need.
A cellular cleaning and recycling system
Under normal conditions, this process occurs at basal levels, that is, at minimum levels at which cell quality is guaranteed. However, it is increased in situations of stress or energy demand. Without oxygen, the cell has no way to obtain energy and therefore autophagy is increased to try to save energy by reusing components. When nutrients are in short supply, autophagy is activated and a double-membrane vesicle forms inside the cell called autofagosoma. It is a kind of cellular garbage bag that encompasses waste (such as misfolded proteins) and sends it to cell organelles called lysosomes. At this time, the lysosomes, thanks to their high digestive enzyme contentare capable of decomposing practically any type of biological material into the small elements that form it.
But there is nothing to be wasted. These broken down pieces become new cellular components that can be used again. For example, a defective protein would be broken down into amino acids, which can be reused to form a new functional protein instead of having to be synthesized from scratch, thus saving energy. Therefore, autophagy, in addition to being a housekeeping system, also functions as a cell recycling system.
There is a type of selective autophagy: xenophagy. Detects microorganisms that have entered the cell, including viruses and bacteria
And there is still more. There is a type of selective autophagy: xenophagiawhich specifically detects microorganisms that have entered the cell, including Virus and bacteria, engulfs them and directs them to autophagosomes for further degradation. It is a form of defense against infections, eliminating pathogens and activating the cells of our immune system. However, some pathogens have learned to ‘hack’ this system, using autophagosomes as replication and/or proliferation sites.
What if autophagy fails?
After knowing all this, it seems that we cannot live without autophagy. And so it is. When this system does not work properly, garbage accumulates in the cells, this can affect their functioning and be very harmful. In fact, it has been shown that when autophagy is altered (either by inactivation or hyperactivation) it gives rise to some neurodegenerative diseases, cardiovascular, autoimmune, metabolic and even various types of cancer.
The Lafora’s disease is an example in which a autophagy failure, although in this case said alteration is not the main cause. At the Institute of Biomedicine of Valencia (IBV) of the CSIC, we investigate this ultra-rare disease that barely affects one person per million inhabitants and that mainly causes epileptic seizures and neurodegeneration. It appears in children and adolescents and, unfortunately, causes the death of patients in just ten years from the appearance of the first symptoms.
Although it is thought that the main cause of the disease It is the accumulation of an abnormal form of glycogen (the molecule where the body stores glucose to be able to use it when it needs immediate energy) in the brain and other tissues, there are alterations at other levels. Failures in autophagy have been detected, but the molecular mechanisms by which this process is deregulated in this disease are still unknown. Autophagy is a highly controlled process, as well as complex, in which many proteins participate that make possible the formation of autophagosomes and the subsequent lysosomal degradation of cellular debris. This implies that the alteration of autophagy can come from failures at different levels of control.
Like most rare diseases, Lafora disease it has no cure. exist more than 7,000 rare diseases and, despite being rare, around 3 million people in Spain suffer from any of them. With research, we will be able to discover the molecular mechanism and achieve appropriate treatments that improve the quality of life of the affected people and even extend their life expectancy and, who knows, perhaps in the future to be able to cure it.
* Laura Baños Carrión is a researcher at Institute of Biomedicine of Valencia of the CSIC.
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