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Autophagy: a cellular defense against cancer unveiled

Nobel Laureate Yoshinori Ohsumi

Village News staff

Autophagy, a cellular process discovered by Japanese cell biologist Yoshinori Ohsumi, emerged as a topic in medical research. This process, initiated during fasting or starvation, involves cells consuming their own components to cope with a lack of nutrients and energy. Yoshinori Ohsumi’s groundbreaking work in unraveling the mysteries of autophagy earned him the Nobel Prize in Physiology or Medicine, and it has since become an area of study in understanding disease prevention and cancer treatment. This article delves into the significance of autophagy and its benefits in fighting cancer.

Understanding autophagy

The term “autophagy” originates from Greek words: “auto” meaning self and “phagy” meaning eating. Essentially, it refers to a cellular process whereby cells degrade and recycle their own damaged or unnecessary components, such as proteins, organelles and even invading pathogens. Autophagy is a natural and essential part of the body’s defense mechanisms, helping maintain cellular homeostasis and ensure optimal cellular function.

How autophagy works

Autophagy is a highly orchestrated process involving a series of steps.

In initiation, cellular stressors, such as nutrient scarcity or oxidative stress, trigger the activation of autophagy. It begins with the formation of a structure known as the phagophore or isolation membrane.

In elongation, the phagophore expands and engulfs the targeted cellular components, forming a double-membrane vesicle called the autophagosome.

In maturation, the autophagosome fuses with lysosomes, which contain digestive enzymes, forming an autolysosome. The contents of the autophagosome are then degraded by these enzymes.

In recycling, the degraded components are broken down into their basic building blocks of amino acids, fatty acids, etc., which are subsequently recycled and utilized to synthesize new molecules or generate energy for the cell.

Autophagy and disease prevention

Autophagy serves as a crucial cellular mechanism for preventing a wide array of diseases. By clearing damaged proteins and organelles, autophagy maintains cellular health and prevents the accumulation of toxic aggregates that could lead to neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.

Moreover, autophagy plays a vital role in bolstering the immune system. It helps eliminate intracellular pathogens and plays a significant part in presenting antigens to immune cells, thus aiding in the body’s defense against infections.

Autophagy and cancer

The connection between autophagy and cancer has been a subject of extensive research in recent years. Cancer is characterized by uncontrolled cell growth and the evasion of cell death mechanisms, both of which heavily rely on disruptions in cellular homeostasis. Autophagy, as a regulator of cellular health, plays a complex role in cancer development and treatment.

In its early stages, autophagy acts as a tumor suppressor mechanism by clearing damaged cellular components and preventing the accumulation of genetic mutations that can lead to cancer initiation. It helps maintain genomic stability and prevents the transformation of healthy cells into cancerous ones.

Paradoxically, once tumors have established, autophagy can also facilitate cancer cell survival. In the harsh microenvironment of solid tumors, nutrients and oxygen are scarce, subjecting cancer cells to metabolic stress. Autophagy allows cancer cells to survive under these conditions, promoting tumor growth and resistance to therapies.

The dual role of autophagy in cancer has sparked interest in developing autophagy-targeted therapies. Researchers are exploring the possibility of modulating autophagy to improve cancer treatment outcomes. One approach involves inhibiting autophagy to sensitize cancer cells to conventional therapies, such as chemotherapy and radiation. Another strategy aims to induce excessive autophagy in cancer cells, pushing them into a state of self-destruction known as autophagic cell death.

Autophagy, a cellular process discovered by Nobel laureate Yoshinori Ohsumi, plays a critical role in maintaining cellular homeostasis and preventing diseases. Its multifaceted nature in cancer development and treatment has captured the attention of scientists worldwide. Understanding the intricate workings of autophagy offers promising avenues for developing innovative and effective cancer therapies, potentially opening new doors in the fight against cancer.

Reference: Mizushima, N. (2018). Autophagy: Process and function. Genes & Development, 30(17), 467-480. doi: 10.1101/gad.283592.116

 

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