Elucidating the mechanisms

Within this research field Aaron Ciechanover, Avram Hershko and Irwin Rose were awarded the 2004 Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation . The proteasome efficiently degrades proteins one-by-one, but this mechanism did not explain how.

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Ohsumi generated yeast lacking vacuolar degradation enzymes. When these yeast cells were starved, autophagosomes rapidly accumulated in the vacuole (middle panel). His experiment demonstrated that autophagy exists in yeast. As a next step, Ohsumi studied thousands of yeast mutants (right.

Elucidating the mechanisms

Intense research is now ongoing to develop drugs that can target autophagy in various diseases. Autophagy has been known for over 50 years but its fundamental importance in physiology and medicine was only recognized after Yoshinori Ohsumi s paradigm-shifting research.

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Elucidating the mechanisms

The cell therefore appeared to have a strategy for delivering large cargo to the lysosome. Further biochemical and microscopic analysis revealed a new type of vesicle transporting cellular cargo to the lysosome for degradation (Figure 1).

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