Autophagy

Article

July 5, 2022

Autophagy is one of the mechanisms that cells have to break down intracellular proteins. It is a mechanism found in eukaryotes from yeast to humans, preventing the accumulation of abnormal proteins in cells, and recycling proteins when excessive protein synthesis or deterioration of the nutritional environment occurs. , It is involved in the maintenance of homeostasis of the living body by eliminating pathogenic microorganisms that have invaded the cytoplasm. In addition, it is known to be involved in programmed cell death in the process of ontogeny, the development of diseases such as Huntington's disease, and suppression of cell canceration. auto- is the Greek prefix for "self" and phagy means "eat", defined by Christian de Duve in 1963. From this background, it is also translated as autophagy.

History

Discovery of lysosomes

From 1953 to 1955, Christian de Duve discovered lysosomes as organelles containing various hydrolases. And in January 1962, autophagy was first observed by Keith Roberts Porter and Thomas Ashhord of Rockefeller University. At this time, since it was discovered in starved rats, it was speculated from the beginning that it was nourished by eating itself and prevented starvation. Later, this guess will be revealed to be correct. In 1963, De Duve named the phenomenon in which cells fuse their proteins into vesicles and fuse them with lysosomes to degrade them, and the vesicles are called autophagosomes. Since then, the elucidation of the proteolytic mechanism by the ubiquitin-proteasome system has progressed, but on the other hand, little progress has been made in the molecular biological elucidation of autophagy. This was largely due to the fact that electron microscopic observation was the only means of detecting autophagosomes. In addition, a paper denying the autophagy phenomenon was also published.

Yeast autophagy

In 1992, Yoshinori Ohsumi (then an assistant professor at the Faculty of Liberal Arts, University of Tokyo) and others observed the autophagy of Saccharomyces cerevisiae for the first time. In 1988, Osumi et al. Confirmed the phenomenon that proteins and other substances were taken up into the vacuole of Saccharomyces cerevisiae, and observations in 1992 demonstrated autophagy in Saccharomyces cerevisiae. Vacuoles are organelles with similar properties to lysosomes and contain a large number of hydrolases, and are the largest compartments in Saccharomyces cerevisiae that occupy more than 25% of the cell volume. Saccharomyces cerevisiae undergoes meiosis and sporulation when the nitrogen source is depleted, but it is known that vacuolar formation deficient in vacuolar hydrolases, and vacuoles are important in nutrient starvation. It was suggested to have a physiological function. Focusing on these things, Osumi et al. Observed the proteolytic enzyme-deficient strain in a starved state. Osumi's conjecture was correct, and he found that small granules that had accumulated in the vacuole without being degraded due to a deficiency of proteolytic enzyme were moving around violently in Brownian motion. Further observations using an electron microscope revealed the following. The granules have been shown to be a monolayer structure and have been named autophagic body. An isolation membrane appears in response to starvation, and as the membrane grows, it surrounds cytoplasmic proteins and forms autophagosomes. Autophagosome