I am delighted that Yoshinori Ohsumi won this year’s Nobel Prize in physiology or medicine. His pioneering work in yeast led to the discovery of genes and biological processes that are needed for autophagy.
Autophagy (from the Greek for “self-eating”) is the mechanism by which cells break down and recycle cellular content. Without this vital housekeeping role we’d be more prone to cancer, Parkinson’s and other age-related disorders.
Although scientists have been aware of autophagy since the 1960s, it wasn’t until Ohsumi’s experiments with yeast in the 1990s that we began to understand the important role of this biological process.
The autophagy process is remarkably similar across lifeforms. One function that is the same, from yeast to humans, is to protect cells against starvation and related stresses. In these conditions, autophagy allows cells to degrade large molecules into basic building blocks, which are used as energy sources. The discovery of key yeast autophagy genes that was led by Ohsumi was particularly powerful because it helped scientists to quickly identify the genes in mammals that have similar functions. This, in turn, has provided vital tools for laboratories around the world to study the roles of autophagy in human health and disease.
With the knowledge that various mammalian genes are needed for autophagy, researchers could then remove these genes from cells or animals, including mice, and examine their functions. These types of studies have highlighted the importance of autophagy in processes including infection and immunity, neurodegenerative diseases and cancer.
The importance of Ohsumi’s findings
My laboratory, for example, found that autophagy can break down the proteins responsible for various neurological diseases, including forms of dementia (caused by tau), Parkinson’s disease (alpha-synuclein) and Huntington’s disease (mutant huntingtin). We are pursuing the idea that by increasing the autophagy process we could potentially treat some of these conditions.
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Another important consequence of Ohsumi’s discoveries is that they allowed subsequent studies that aimed to understand the mechanisms by which autophagy proteins actually control this process. Indeed, Ohsumi’s group have also made seminal contributions in this domain.