on June 20, 2012
The scientific journal Molecular Cell publishes in its issue of June 29 the results of a study conducted by the group of Professor Maurizio Molinari from the Institute for Research in Biomedicine (IRB), Bellinzona, made in collaboration with the group of Professor Fulvio Reggiori from the University Medical Center Utrecht.
The study describes a mechanism used by our cells to prevent an outbreak of stress that would otherwise inevitably lead to death.
The cells are real “protein factories”, producing several thousands of proteins with diverse functions, which allow us, as few examples, to see, hear, digest what we eat, carry oxygen in the blood, protect our body from viruses and bacteria. Proteins that do not adopt the correct structure can form aggregates and cause stresses that kill cells. Such stresses are the cause of several human diseases such as Alzheimer’s, Parkinson’s diseases, cystic fibrosis, and a whole series of more or less rare hereditary diseases with fatal course. Depending on the affected organ, these diseases may cause among others the loss of cognitive function, liver and lung failures, vision loss and represent an enormous medical and social cost.
The work carried out at the IRB by Riccardo Bernasconi, Carmela Galli, Julia Noack and Siro Bianchi under the guidance of Dr Molinari was financed by the Gabriele Foundation, the San Salvatore Foundation, the Foundation for the Study of Neurodegenerative Diseases and by the Swiss National Science Foundation. The study identified a series of rapidly turned-over “molecular scavengers” (or degradative chaperones) that in healthy cells are almost absent. The accumulation of misfolded proteins retains these “molecular scavengers” in the cells thus promoting their intervention to rapidly disassemble the toxic aggregates thereby preventing the induction of lethal stress. This new mechanism of cellular defense discovered at the IRB was christened ERAD tuning (or adjustment of degradation) and joins the defense mechanisms discovered over twenty years ago and called unfolded protein response (UPR). The results obtained from the group of Dr. Molinari show that ERAD tuning regulates the cellular homeostasis, thus the maintenance of a balanced protein synthesis in healthy cells, while the UPR is induced by problems that persist in time and that cause stress which may lead to cell death.
In this study published in Molecular Cell the groups from Bellinzona and Utrecht also show how some viruses (such as the lethal coronaviruses) can infect our cells seizing the mechanisms that regulate ERAD tuning. These data show that the basic research on the regulation of cellular functions mechanisms may not only enable the development of therapeutic approaches against diseases caused by protein aggregates, but also against diseases caused by pathogens that exploit these mechanisms to infect our body.
Bernasconi, R., Galli, C., Noack, J., Bianchi, S., deHaan, C.A.M., Reggiori, F. and Molinari, M. (2012) Role of the SEL1L:LC3-I complex as an ERAD tuning receptor in the mammalian ER Mol Cell 46: 1-11 (online may 24, 2012, printed in the edition of June 29, 2012).
