LONG before the green movement existed, evolution discovered the virtues of recycling. Cells cannot afford to waste materials, so they disassemble worn-out components for reuse. This happens in subcellular structures called lysosomes, which are bubble-like vesicles filled with digestive enzymes and surrounded by fatty membranes.
Moreover, in an emergency, even components that are still working may be recycled in this way to provide energy needed to keep a starving cell alive, rather as someone facing extremely cold weather may choose to burn his furniture rather than freeze to death. The process is called autophagy (from the Greek for “self-eating”), and the elucidation of its details has been the life’s work of Yoshinori Ohsumi of the Tokyo Institute of Technology (pictured above), who is the winner of this year’s Nobel prize for physiology or medicine.
Before Dr Ohsumi’s studies, biologists knew that autophagy was a two-step process. First, the cellular components to be recycled are enclosed in a fatty membrane to create another type of vesicle, an autophagosome. Then the autophagosome merges with a lysosome, and the lysosome’s enzymes break up the autophagosome’s contents. The details of the process, though, were not known. In particular, how autophagosomes formed was a mystery. It is for supplying those details that Dr Ohsumi has been awarded the prize.
He began his prize-winning work in 1988, looking at autophagy in yeast. This is a well-studied organism, often used by biologists to examine fundamental cellular processes. Unfortunately, its cells are small and to start with Dr Ohsumi could not easily distinguish the autophagosomes within them under a microscope. He dealt with this difficulty by disabling the manufacture of the lysosomic digestive enzymes. That meant autophagosomes were no longer destroyed, and accumulated to the point where they could be seen and studied—especially if a cell was starved, in order to encourage autophagy.
This work, published in 1992, was the key to the rest—the identification of the genes involved in autophagosome assembly, and thus an understanding of how these vesicles come into being. Here, Dr Ohsumi’s choice of yeast paid off. The yeast genome was already well understood when he started his work, and was also one of the first to be elucidated in its entirety as part of the Human Genome Project. By knocking out genes so that they stopped working and then examining the consequences of their absence, he was able to build up a complete picture of the process by which autophagosomes are put together. And, though yeast and humans are not closely related, autophagy is such a fundamental cellular process that its course in the two species is more or less the same, so yeast autophagy is a good model of its human equivalent.
Dr Ohsumi’s work, moreover, has wider ramifications than merely illuminating an important piece of cellular housekeeping. It also helps explain how invading bacteria and viruses are dealt with (for such unwelcome guests are also gobbled up by autophagosomes), and shines light on diseases, including Parkinson’s and some sorts of diabetes, caused when autophagy goes wrong and cellular rubbish accumulates.