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Spotlight On: Autophagy

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Defects in autophagy have been linked to several diseases, including cancer, neurodegeneration, and infectious and immunological diseases. The significance of this process was highlighted in 2016 when Yoshinori Ohsumi, PhD, was awarded the Nobel Prize in Physiology or Medicine for his decades-long research on autophagy. You might already be wondering: What is autophagy and why is it so important?

The word autophagy has roots in ancient Greek: “auto” (self) and “phagy” (eating) or “self-eating.” Autophagy is a process in which cells surround damaged proteins or structures called organelles in a membrane. The cells then fuse with an organelle that contains enzymes, called the lysosome. The contents of the lysosome are acidic and similar to the acids in the stomach. The enzymes break down proteins into their smaller parts, such as amino acids, so they can be reused as parts for new proteins or as a source of energy.

Ohsumi’s work led to the discovery of the many genes that are involved in regulating autophagy and revealed that autophagy is essential for cells to survive in poor nutrient conditions. A good example of this is when babies are born. Newborns need lots of energy, but at birth, they stop being fed via their umbilical cord. To help babies survive the short period before they start feeding, autophagy kicks in to give them the energy they need. 

Even without food supply problems, autophagy is necessary for our cells and organs to function properly. When they work normally, cells can make mistakes that lead to defective proteins, which need to be removed from the body. Sometimes, mitochondria—the energy factory of the cells—is damaged, which could lead to toxic molecules being released. But autophagy can keep this from happening. Think of autophagy as an essential cellular housekeeping process that prevents the accumulation of damaged proteins and organelles that would otherwise lead to cell death.

Autophagy also fights bacterial and viral infections by delivering the pathogens to the lysosome, where they are destroyed. However, many viruses and bacteria have developed tools that stop autophagy so they can continue to live. For example, SARS-CoV-2, the virus that causes COVID-19, blocks a key step in the autophagy pathway and could be important for the virus’ survival and replication.

Studies have found that people have reduced autophagy as they age. This may factor into why cancer, heart disease and Alzheimer’s disease are more common in older adults. Scientists are studying whether using medications to stimulate autophagy could improve our health span.

So, while the phrase “self-eating” may sound gross, remember, autophagy is actually a good thing.

John Chatham, DPhil, FAPS, is a professor of pathology in the Division of Molecular and Cellular Pathology at the University of Alabama at Birmingham.

 

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