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Autophagy: The Self-Cleansing Process That Keeps Your Body Healthy

Autophagy is a self-cleansing process that occurs in all cells in the body. The word autophagy comes from the Greek autós, meaning “self”, and phagein, meaning “to eat”. This process is essential for the recycling of damaged proteins and organelles, as well as for the removal of pathogens.  Autophagy was first described in the late 1950s, but its molecular mechanisms were not elucidated until the early 21st century. In 2016, Japanese scientist Yoshinori Ohsumi was awarded the Nobel Prize in Physiology or Medicine for his discoveries of the mechanisms of autophagy. Autophagy occurs in response to various stresses, such as nutrient deprivation, oxidative stress, and temperature changes. It is also involved in developmental processes, such as cell growth, differentiation, and death. In certain disease states, such as cancer and neurodegeneration, autophagy is dysregulated. This blog will provide an overview of autophagy, its molecular mechanisms, and its physiological functions. What is A

Yoshinori Ohsumi Japanese biologist

Yoshinori Ohsumi Japanese biologist

Yoshinori Ohsumi (born February 9, 1945 in Fukuoka, Japan) is a Japanese cell biologist who pioneered the study of autophagy, the process by which cells destroy and recycle proteins and other cellular components. Ohsumi's research was essential in uncovering autophagy's critical physiological functions, such as its role in helping cells adapt to various types of stress, contributing to embryo development, and removing damaged proteins. Ohsumi was awarded the Nobel Prize in Physiology or Medicine in 2016 for his work on autophagy.

From a young age, Ohsumi was fascinated by natural sciences. He traveled to Rockefeller University in New York as a postdoctoral researcher with American physical chemist Gerald Maurice Edelman after getting a B.S. degree in 1967 and a Ph.D. in 1974 from the University of Tokyo. Ohsumi began by developing a technique for mouse in vitro fertilization. He became interested in vacuoles (membrane-bound fluid-filled organelles), which were easily acquired from yeast cells and in which Ohsumi had seen several transport routes for transferring molecules across the vacuole membrane, despite his lack of experience with mammalian embryonic development.

Ohsumi returned to the University of Tokyo in 1977 to take up a job as a junior professor in the biology department. He returned to the subject of vesicle physiology in 1988, after establishing his own laboratory there, focusing in particular on the lytic (degradation) activities of vacuoles in yeast, about which little was known at the time. But, in animal cells, drastic cellular disintegration processes known as autophagy, or "self-eating," had already been identified and studied extensively, providing Ohsumi with a starting point for his research. The discovery that autophagy could be initiated in animal cells by exposing them to nutrient-deficient conditions was particularly significant.

In a separate experiment, Ohsumi altered the yeast Saccharomyces cerevisiae to lack vacuolar proteinase and peptidase enzymes (preventing sporulation) and then starved the yeast cells of nutrition. Under a light microscope, he discovered that autophagic entities had gathered inside the vacuoles of the yeast. In 1992, he presented his findings, which were the first to show the occurrence of autophagy in yeast.


WHAT YOU SHOULD KNOW ABOUT AUTOPHAGY



Soon after, Ohsumi used his genetically modified yeast to find autophagy-related genes. The roles of 14 autophagy genes in yeast were finally discovered and defined by researchers in his group. They discovered that enzymes expressed by some of the genes had been conjugated (linked together), indicating that yeast had a complete autophagic pathway. Furthermore, several of the genes were homologous to mammalian genes, implying that human cells have a corresponding mechanism. Later studies by Ohsumi revealed the mechanism of autophagosome formation (the vesicle that engulfs cellular components and carries them to the lysosome, where they are degraded) and the function of stress in autophagy initiation.

Ohsumi's research was crucial in understanding how cells discard worn-out protein complexes and organelles that are too massive to be destroyed by other mechanisms. The aberrant buildup of such components is extremely harmful to cells and has been linked to a variety of illnesses. As a result, Ohsumi's results have important implications for understanding and treating a variety of illnesses in which autophagy is altered, such as cancer, Parkinson's disease, and type 2 diabetes.

Ohsumi has received a number of accolades and honors throughout his career, including the Canada Gairdner International Award (2015), the Keio Medical Science Prize (2015), and the Rosenstiel Award (2015).