Researchers from Argentina and the United States described a new regulatory mechanism for the pathway used by the cell to recover molecules and nutrients when it undergoes adverse conditions. Failures in this process are associated to pathologies such as cancer or neurodegenerative conditions.
Broadly speaking, when the cell detects a lack of nutrients, it decides to ‘eat itself’ and recycle components. This process is known as autophagy, and Yoshinori Ohsumi was awarded with the Nobel Prize in Physiology or Medicine in 2016 for this discovery.
A new study recently published in e-Life and co-coordinated by Mario Rossi, group leader of the ‘Autophagy and Ubiquitin / Proteasome System’ group of IBioBA, and Michele Pagano, from the University of New York, United States, describes and analyzes a new molecular mechanism that the cell uses to regulate this recycling.
“One of the main questions in relation to autophagy is: Where do the membranes that the cell needs for this process come from?”, explains Rossi, independent researcher of CONICET at the Biomedicine Research Institute of Buenos Aires (IBioBA, CONICET – Partner Institute of the Max Planck Society).
When autophagy starts, the cell generates large vesicles surrounded by membranes that capture material from the cytoplasm and transport it to degradation sites, where the components are recycled.
But to tell the story of this finding it is important to know the molecules involved:
Pero para contar la historia de este descubrimiento hay que nombrar primero a los participantes:
- ULK1: protein that is one of the great regulators of autophagy. It plays a role at the beginning of the process and affects the entire cascade of events.
- COPII: protein complex that covers the vesicles that transport molecules withinthe cell. Until now its role in autophagy was not known.
- SEC23B: one of the proteins of COPII.
Researchers found that when nutrients are poorly avaiñable the cell needs to activate this recycling pathway, ULK1 prevents SEC23B from degrading and ‘recruits’ it to work in autophagy. With increased amounts of SEC23, more COPII is formed, which in turn increases the amount of vesicles and membranes available for autophagy.
“This research is in line with a series of very recent studies that demonstrate the existence of a strong connection between the formation of COPII vesicles and autophagy. For example, it was demonstrated that certain mutations in SEC23 produce effects in some human diseases, and that they could be at some point associated with alterations in the autophagic pathway”, analyzes Rossi.
“It is known that this pathway plays a role in cellular balance and is related to many diseases, such as cancer or nervous system pathologies. Thus, to understand how autophagy works and is regulated has a very important value from the predictive point of view”, he adds.