The 2016 Nobel Prize in Physiology or Medicine has been awarded to Dr. Yoshinori Ohsumi, a scientist who discovered and studied the mechanisms of autophagy – or how a cell can destroy and recycle its own contents.
Dr. Yoshinori Ohsumi, a researcher who discovered and studied the process of autophagy, has been awarded the 2016 Nobel Prize in Physiology or Medicine. Autophagy, a term with Greek origins that means ‘self-eating’, is the process by which a cell can destroy and recycle materials taken up from outside of the cell or its own proteins, DNA, lipids (fat), or carbohydrates. This process provides the cell with energy, nutrients, and the building blocks needed to make other cell components.
Foundational research from the 1950s and 1960s showed that human cells have lysosomes, or specific cellular compartments that contain enzymes to digest damaged or unwanted cell materials. Under the microscope, lysosomes were observed to have large amounts of cell content and even whole cellular compartments that were delivered by a vesicle, which was termed an autophagosome. Cell components were enveloped by autophagosomes as they formed, and were brought to the lysosome to be destroyed.
Upon starting his lab in 1988, Ohsumi set out to examine protein degradation using baker’s yeast, or Saccharomyces cerevisiae. This type of yeast has cells with vacuoles, a cell component that corresponds directly to lysosomes in humans cells. Yeast are model organisms for studying biological processes since they are less complex and inexpensive, and many of their genes can be linked to corresponding human ones. Unsure as to whether autophagy existed in yeast, Ohsumi developed an experimental strategy where he would disrupt protein degradation by mutating the enzymes responsible for destroying proteins in vacuoles. He hypothesized that if yeast used the process of autophagy, large autophagosomes would accumulate in vacuoles. Autophagosomes filled vacuoles within a few hours to support his hypothesis.
Ohsumi’s experiment proved that autophagy occurs in yeast cells and he published his results in 1992 in the Journal of Cell Biology. In 1993, he identified the key genes critical to this process by exposing yeast to a gene mutation-inducing chemical and creating a yeast mutant that was unable to undergo autophagy when stimulated. His following work examined the molecular mechanisms of autophagosome formation.
Research by scientists following in Ohsumi’s footsteps has discovered that autophagy can fight infections by eliminating bacteria and viruses, as well as counteract aging by degrading damaged proteins. Disruption of this process has also been correlated with Parkinson’s disease, type 2 diabetes, and other chronic diseases related to aging. Ohsumi’s pioneering research in autophagy has led to an understanding of the key physiological processes required for the breakdown and recycling of cellular components. Deservedly, his work has earned him the highest honour in medicine and research.
Written By: Fiona Wong, PhD