Autophagy

Autophagy is a normal biological process in which cells break down to allow for the removal and recycling of defective or degraded parts or parts that are no longer needed. It is an essential part of maintaining cell health. Without it, cells would become cluttered with unnecessary material that would affect their function. When the process does not work correctly, it can lead to disease. Disruptions in the normal autophagy process are thought to be possible factors in cancer, osteoarthritis, various forms of dementia, Huntington's disease, and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Researchers hope that uncovering more about how the process works can lead to new treatments or cures for these health conditions.

Background

The word autophagy comes from the Greek words auto, meaning "self," and phagy, meaning "eating." Combined, they describe the self-consuming process of autophagy, which is present in humans and many other life-forms. Although it seems self-destructive, the process is essential to many normal and beneficial functions, including immune responses and efforts to minimize the effects caused by a lack of nutrients, or starvation.

Christian de Duve, a British-born Belgian biochemist who was studying how insulin works in the mid-1960s, named the process. While others had observed the process, de Duve was the first to determine where in the cells it occurred. He initially believed his observation to be of little consequence. However, what he noticed about the autophagy process led him to discover lysosome and peroxisome, two organelles or cell structures with very specific functions. The two are important parts of the metabolic process, or the generating of energy as fuel for the body. De Duve shared the 1974 Nobel Prize in Physiology or Medicine for his work.

The discovery of the two organelles provided researchers with great insight into the autophagy process. Other researchers would build on the work done by de Duve to identify the genes responsible for initiating the autophagy process and gain a better understanding of how the process works. One of these researchers was Japanese cell biologist Yoshinori Ohsumi. Ohsumi conducted experiments with yeast that revealed key details about autophagy and its role in cell health. These experiments also examined the role of autography in the formation of a number of diseases, especially the degenerative diseases of aging, such as arthritis and dementia, and neurological conditions, such as Huntington's and Parkinson's diseases. For his efforts, Ohsumi was awarded the 2016 Nobel Prize in Physiology or Medicine.

Overview

Autophagy occurs on an ongoing basis in the cells of all life-forms. In most cases, it occurs at exactly the rate that is needed for cells to rid themselves of waste components so new ones can be formed. It is essentially the cell's waste recycling process. The trigger for this is usually when the cell recognizes it is running out of nutrients. The autophagy process is initiated so the cell's components can be used for energy, and those that are depleted or that have become damaged or unusable for a variety of reasons can be eliminated.

Once the process is initiated, a double membrane surrounds and isolates the portion of the cell to be broken down and consumed. The membrane and its contents, which includes a cellular fluid known as cytosol, become known as an autophagosome. The autophagosome attaches to a lysosome. Lysosomes, one of the organelles discovered by de Duve, contain enzymes that digest the autophagosome and its contents. These contents can include parts of the cell as well as invaders such as bacteria and viruses. A difference in the level of acidity between the lysosome and the rest of the cell helps to protect the cell from the effects of the lysosome enzymes should any leak during the autophagy process. Once all the waste products inside the autophagosome are taken up by the lysosome, the enzymes digest them and prepare them for recycling. Through this process, they provide a new energy source for the cell and help maintain the cell's overall health.

The process is complex and requires a precise series of steps. While the lysosomes are an integral part of the process, they do not control it. Instead, special proteins from the cell determine what parts of the cell need to be recycled, and the lysosomes provide the means to carry out the process.

The autophagy process is so important to cell health that disruptions in the process have been identified as a factor in a number of diseases. Research has indicated that abnormal clumps of protein and other excess cell material trigger inflammation that leads to many health problems. Efforts to remove these proteins and other inflammatory substances through medical intervention have been unsuccessful, so researchers are looking for ways to encourage the natural autophagy process to target them instead.

In addition to serving as a cleaning process for excess cell materials, autophagy serves several other purposes. The process can help cells survive starvation when nutrients become scarce by recycling materials from within the cell into new nutrients. It is also part of a process known as autophagic cell death or programmed cell death (PCD). This is the planned death of cells after they have completed their function or outlived their usefulness.

Although autophagy results in many benefits for the health of cells, it is not always a good thing. For example, the process can make it easier for some forms of bacteria to grow and attack a host. Researchers attempting to manipulate the autophagy process need additional study to take into account the potential repercussions of encouraging the process and determine the ways the process can provide the greatest benefit with the least risk.

Bibliography

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