Introduction
Yoshinori Ohsumi, a Japanese cell biologist, was awarded the 2016 Nobel Prize in Physiology or Medicine for his groundbreaking discoveries on autophagy, a fundamental process in cells. Autophagy, derived from the Greek words for "self-eating," is how cells recycle and degrade their components. Ohsumi's work has revolutionized our understanding of how cells maintain themselves, respond to stress, and how disruptions in autophagy contribute to various diseases.
The Discovery of Autophagy and the Lysosome
The story of autophagy begins in the mid-1950s with the discovery of lysosomes, specialized organelles within cells that contain enzymes for digesting proteins, carbohydrates, and lipids. Christian de Duve, a Belgian scientist, received the 1974 Nobel Prize in Physiology or Medicine for discovering the lysosome. Researchers observed in the 1960s that large cellular components and even whole organelles could be found inside lysosomes under certain conditions. This led to the discovery of autophagosomes, vesicles that transport cellular cargo to the lysosome for degradation. Christian de Duve coined the term autophagy, or "self-eating," to describe this process.
Ohsumi's Groundbreaking Research in Yeast
Yoshinori Ohsumi began his work on autophagy in 1988, focusing on protein degradation in the vacuole, an organelle in yeast cells analogous to lysosomes in human cells. Ohsumi reasoned that if he could disrupt the degradation process in the vacuole while autophagy was active, autophagosomes would accumulate and become visible under a microscope. He cultured mutated yeast lacking vacuolar degradation enzymes and stimulated autophagy by starving the cells. The results were remarkable: within hours, the vacuoles were filled with small vesicles that had not been degraded. These vesicles were autophagosomes, and Ohsumi's experiment proved that autophagy exists in yeast cells.
Ohsumi then engineered yeast strains in which autophagosomes accumulated during starvation. He exposed these yeast cells to a chemical that randomly introduced mutations in many genes and then induced autophagy. Within a year of his discovery of autophagy in yeast, Ohsumi had identified the first genes essential for autophagy. He functionally characterized the proteins encoded by these genes in subsequent studies.
The Significance of Ohsumi's Findings
Ohsumi's research revealed that autophagy is not simply a response to starvation but also contributes to a range of physiological functions, such as inhibiting cancer cells and aging, eliminating pathogens, and cleaning the insides of cells. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as adaptation to starvation or response to infection.
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After the machinery for autophagy was identified in yeast, it became clear that virtually identical mechanisms operate in our own cells. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components and is therefore essential for the cellular response to starvation and other types of stress. After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation.
Autophagy and Disease
Disturbances in autophagy have been linked to various diseases, including Parkinson's disease, type 2 diabetes, Alzheimer's disease, certain cancers, and many infections. Mutations in autophagy genes can cause genetic disease. Too little autophagy is a common problem during old age. Diseases like Alzheimer's and type 2 diabetes appear as our cells fail to clear out their gunk.
Recent data indicate that autophagy plays an essential role in the inflammatory pathways in allergy and asthma. Autophagy has been linked to the pathogenesis of asthma. There are data available linking autophagy in airway epithelium, and autophagy might be essential for bronchial epithelial mucus secretion, as has been shown in an allergic asthma model. A link between the epithelial-mesenchymal transition unit and autophagy has been shown in other models of allergic asthma. A further link between autophagy and asthma has been established for human rhinovirus, respiratory syncytial virus, coronavirus, adenovirus, and influenza A virus through the role of autophagy in the defense against respiratory tract viruses, which represent a major exacerbation factor for asthma.
Autophagy and Fasting
Scientists have found that fasting for 12+ to 24+ hours triggers autophagy and is thought to be one of the reasons that fasting is associated with longevity. There is a large body of research that connects fasting with improved blood sugar control, reduced inflammation, weight loss, and improved brain function; Ohsumi’s research provides some of the "how" to this research.
Sporadic short-term fasting, driven by religious and spiritual beliefs, is common to many cultures and has been practiced for millennia, but scientific analyses of the consequences of caloric restriction are more recent. Published studies indicate that the brain is spared many of the effects of short-term food restriction, perhaps because it is a metabolically privileged site that, relative to other organs, is protected from the acute effects of nutrient deprivation, including autophagy. Short-term food restriction induces a dramatic upregulation of autophagy in cortical and Purkinje neurons.
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Misinformation Regarding Ohsumi and Fasting
False social media posts with tens of thousands of shares worldwide claim that Yoshinori Ohsumi recommended fasting to cure cancer. However, there is no evidence that he made the remarks in the posts.
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