Friday, June 9, 2023

Autophagy or how waste is removed from our cells

From the time of waking up to sleeping, man continuously produces garbage. Getting rid of it is a simple and everyday task, and we find a container where we can throw it a few steps away 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 autophagy, a word that comes from the Greek and means “to eat oneself.”

Autophagy is the way cells maintain themselves in optimal and healthy conditions, avoiding the accumulation of waste products that can affect their functionality. It is a cleaning system by which, as if they were a vacuum cleaner, cells swallow up dirt, which in their case is all those cellular components and damaged proteins that do not work properly or that they do not need. No longer required.

A cellular cleaning and recycling system

Under normal conditions, this process occurs at basal levels, that is, at the minimum level at which cell quality is guaranteed. However, it increases in situations of stress or energy demand. Without oxygen, the cell has no way to obtain energy and so autophagy is increased to try to conserve energy by reusing components. When nutrient supply is low, autophagy is activated and a double-membrane vesicle called an autophagosome forms inside the cell. It is a type of cellular garbage bag that incorporates waste (such as misfolded proteins) and transports it to cell organelles called lysosomes. At this time, lysosomes, thanks to their high content of digestive enzymes, are capable of breaking down practically any type of biological material into the smaller elements that make up it.

But there’s nothing to waste. These broken down fragments become new cellular components that can be used again. For example, a defective protein will be broken down into amino acids, which can be reused to make a new functional protein instead of synthesizing it from scratch, thus saving energy. Therefore, autophagy, in addition to being a scavenging system, also functions as a cellular recycling system.

There is one type of selective autophagy: xenophagy. Detects microorganisms entering the cell, including viruses and bacteria

There is so much more. There is one type of selective autophagy: xenophagy, which specifically detects microorganisms that have entered the cell including viruses and bacteria, engulfs them and directs them into autophagosomes for subsequent degradation. It is a form of protection against infections, elimination of pathogens and activation of cells of our immune system. However, some pathogens have learned to ‘hack’ this system by using autophagosomes as replication and/or dissemination 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, waste accumulates in the cells, this can affect their functioning and can be very harmful. Indeed, it has been shown that when autophagy is altered (either by inactivation or hyperactivation) it gives rise to certain neurodegenerative, cardiovascular, autoimmune, metabolic diseases and even various types of cancer.

Lafora disease is an example in which autophagy fails, although in this case the mutation is not the main cause. At the Institute of Biomedicine of CSIC’s Valencia (IBV), we investigate this ultra-rare disease that affects barely 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.

Autophagy or how waste is removed from our cells

Although it is believed that the main cause of the disease is the accumulation of an abnormal form of glycogen (the molecule where the body is able to use glucose when it needs energy urgently) in the brain and other tissues, there are changes in other levels. . Failures in autophagy have been detected, but the molecular mechanisms by which this process is regulated in this disease are still unknown. Autophagy is a highly regulated 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 alteration of autophagy may come from failures at different levels of control.

Like most rare diseases, there is no cure for Lafora disease. There are more than 7,000 rare diseases and, despite being rare, about 3 million people in Spain suffer from one of them. With research, we will be able to discover the molecular mechanisms and find suitable treatments that improve the quality of life of those affected and even increase their life expectancy and who knows, maybe in the future. be able to fix it.

*Laura Banos Carrion is a researcher at the CSIC Institute of Biomedicine in Valencia.

Tags: autophagy, the autophagosome, bacteria, biomedicine, cell, CSIC, CSIC dissemination, scientific culture, dissemination, Lafora disease, rare disease, Biomedicine Institute of Valencia, lysosome, cell recycling, virus, xenophagy | Archived in: Biomedicine & Health

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