In times of starvation, cells tighten their belts: they start to digest their own proteins and cellular organs. The process - known as autophagy - takes place in special organelles called autophagosomes. It is a strategy that simple yeast cells have developed as a means of survival when times get tough, and in the course of evolution, it has become a kind of self-cleaning process. In mammalian cells, autophagosomes are also responsible for getting rid of misfolded proteins, damaged organelles or disease-causing bacteria.
If this process malfunctions, it can result in infectious diseases, as well as cancer, Parkinson's or Alzheimer's disease. Biochemists at Frankfurt's Goethe University, working together with scientists from the University of Troms in Norway, the Weizmann Institute in Israel and the Tokyo Metropolitan Institute in Japan have just come up with an explanation as to how autophagosomes know exactly which proteins and organelles they should degrade.
"Although autophagy has been known for more than 30 years, it is astonishing that no-one thought of looking for the receptors that make this process so selective" explains Prof. Ivan Dikic from the Institute of Biochemistry II and the Cluster of Excellence 'Macromolecular Complexes' in Frankfurt. He had a head start in this field, since over several years, he and his group have researched and now published their work on another self-cleaning process in the cell: the degradation of small proteins in the proteasome, which acts as a kind of molecular shredder.
"We know that the molecules which are destined to be discarded are marked with the small protein ubiquitin and this is recognised by a receptor located at the gateway to the proteasome. It was natural to suggest a similar recognition mechanism for protein degradation by autophagosomes", says Dikic.
Unlike the proteasome, which is a complex molecular machine, autophagosomes simply consist of a double membrane that fl
|Contact: Ivan Dikic|
Goethe University Frankfurt