The 2016 Nobel Prize in Physiology or Medicine was on Monday awarded to Japanese cell biologist Yoshinori Ohsumi for his work uncovering the mechanisms by which cells “eat” bits of themselves – called autophagy.
His work built on that which won Aaron Ciechanover, Avram Hershko and Irwin Rose the chemistry Nobel in 2004. In the 1970s and 80s they were part of a field of work that uncovered the system that breaks down proteins one by one.
But they could not explain how cells dealt with big proteins and worn-out components.
Autophagy was the answer. Ohsumi’s discoveries led to understanding how cells, for instance, respond to starvation and infection. Mutations in autophagy genes can cause disease, including cancer and neurological disorders.
In human cells, little pockets called lysosomes break down bits that the cell no longer needs. (Lysosomes were discovered by Christian de Duve who shared in the 1974 medicine Nobel.)
Ohsumi started his own lab in 1988 when he focused on protein degradation in a part of a yeast cell called the vacuole – the yeast’s version of a lysosome.
The challenge, though, was to pick out the minuscule components inside a tiny yeast cell – when he started he didn’t even know if yeasts had vacuoles. Microscopes weren’t as powerful as they are today and it was tricky making out the innards of such small cells.
He thought if vacuoles did exist, and he disrupted the enzymes that dismantle proteins, he should see special compartments called autophagosomes – which carry material destined for recycling – accumulate within the cell.
So he cultured mutated yeast and sent them into starvation mode. Sure enough, within hours he saw autophagosomes arise and stay there, as without the enzymes they weren’t able to be broken down.
Within a year of this experiment he discovered the first genes behind autophagy. And it soon became obvious the same mechanism took place in our own cells.
Ohsumi is now at the Tokyo Institute of Technology. But thanks to his decades of work, scientists now know that autophagy can produce fuel and building blocks for cells in times of starvation.
Autophagy can also let cells eliminate invading microbes and discard damaged proteins or components.
Disruptions in the autophagy process has been linked to Parkinson’s disease, cancer and type 2 diabetes.So research is underway to develop drugs that target autophagy mechanisms in those diseases.
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