The 2016 Nobel Prize in Physiology or Medicine has been awarded to Professor Yoshinori Ohsumi (Tokyo Institute of Technology) for the discovery of the mechanism for autophagy, one of the key ways in which the cells in our body destroy and recycle unwanted or damaged cellular material.
What is autophagy?
In order for the cells in our body to function correctly, they continually renew the vital internal machinery necessary for them to survive. To balance this, there must exist processes by which our cells can dispose of the waste products they produce. Autophagy, derived from the Greek “auto- “(self) and “phagein” (to eat), is one such process by which the cell can target these defective and unwanted materials, such as damaged cell components and aggregated proteins, and ensure that they are scrapped. Autophagy can therefore be described as the controlled digestion of internal cell components. It is a normal physiological process which occurs in all eukaryotic organisms, from simple unicellular organisms (such as yeast) to complex multicellular organisms (such as plants and animals).
How does autophagy work?
The general mechanisms of autophagy are thought to be highly similar in all eukaryotic organisms. Defective cell components are engulfed by a membrane, which wraps around the waste material sealing it inside a vesicular structure called an autophagosome. The autophagosomes then transport their cargo to lysosomes; special compartments in our cells which are highly acidic and contain enzymes that can break down unwanted cellular material. The waste cargo is transferred from the autophagosomes to the lysosomes where it is degraded. The small molecules produced from this degradation in the lysosome are then available to the cell to reuse.
Levels of autophagy in cells increase when they are exposed to increased internal stresses, such as an accumulation of waste material. Likewise, just as autophagy helps cells to survive internal stresses, it has a crucial role in enabling cells to cope with external stresses such as a lack of available nutrients. When cells are starved, levels of autophagy increase as cells break down internal components and recycle the products of this degradation to ensure essential processes are preserved. Autophagy therefore has a key role in aiding cells to maintain normal functions and survive under changing environmental conditions.
Why is autophagy important?
Autophagy is a fundamental cellular process which is thought to impact upon a wide variety of different diseases, including neurodegenerative disorders and cancer. It has also been shown to be important in cellular defence against pathogenic microorganisms and viral infection. It should be noted that the role of autophagy in disease is often a highly complex combination of both protective and deleterious effects. For example, in some cases it can assist in defence against invasive pathogens. Conversely, a number of microorganisms specifically exploit the autophagy process as part of their replication cycle. The ability to modulate and control specific stages of the autophagy process in disease states therefore offers great potential for therapeutic interventions.