ETH Zurich biochemists have discovered a new pathway by which the cell selectively degrades ribosomes. The pathway is called ribophagy and will probably enter the textbooks. Ubiquitin makes it all possible.
Ribosomes are the cell’s translation engines. They use genetic information to build chains of amino-acids that afterwards fold to form proteins. The construction of ribosomes in the cell nucleus and the translation work they perform are among the cell’s most energy-intensive processes. During periods of energy shortage the cell needs to save energy and materials and must be able to adapt rapidly to changing environmental conditions. This means that the ribosomes must be taken out of circulation as quickly as possible to halt the translation and protein building. This makes amino-acids available to the cell as components of the proteins needed to maintain homeostasis, i.e. the cell’s equilibrium.
ETH Zurich researchers from the Institute of Biochemistry have discovered a new metabolic pathway used by starving yeast cells to dispose of ribosomes very quickly and selectively. The cells do this by using a novel autophagy process which the biochemists have named “ribophagy”. This mechanism was described recently in “Nature Cell Biology” and is one of the cell’s few known selective autophagy processes, at least according to “textbook knowledge”. For example mitophagy, the degradation of mitochondria, was already known. Biologists use the word “autophagy” to describe the degradation of cellular constituents inside the cell itself.
In ribophagy the ribosome’s two sub-units are first of all separated. The larger of the two, sub-unit S60, is labelled for selective degradation by an enzyme, a protease, cleaving a molecule of ubiquitin from the ribosome or from a protein that interacts with it. A transport vesicle ingests the S60 and carries it to the cell vacuole, where numerous enzymes dismantle the sub-unit into its individual components.
A connection with nerve degeneration
The fact that the cell uses ubiquitin as a label and/or regulator for an autophagy process is also new. Claudine Kraft, a post-doc in Professor Matthias Peter’s group, stresses that “Mono-ubiquitination had never before been found as a ‘labelling’ in an autophagy process. The signalling mechanism controlling the elimination of S40 is still unknown. What is clear is that this sub-unit is also selectively degraded.
According to Claudine Kraft, the cross-link between autophagy and proteosome activity is noteworthy. In recent years scientists have discovered that both processes play an important part in neurodegenerative diseases. Therefore ribophagy is another piece in the jigsaw towards a better understanding of diseases such as Alzheimer’s or Parkinson’s.
Journal reference: Kraft, C., A. Deplazes, M. Sohrmann, M. Peter: Mature ribosomes are selectively degraded on starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease, Nature Cell Biology 10, 5. doi:10.1038/ncb1723
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