Autophagy and mechanical stress

Autophagy is a mechanism by which cells generate vesicles de novo in the cytoplasm, in order to capture and degrade their internal components. This plays many important roles; from allowing the cell to recycle nutrients and survive starvation, to removing the damaged proteins and organelles that wear out over time and accumulate with age.  Autophagy also allows the cell to capture intracellular pathogens when infected. After formation, autophagosomes fuse with the lysosomal system to degrade whatever they have captured.

autophagy diagram
Autophagosomes as initiated and expand in the cytoplasm, capturing unwanted components before fusion with the lysosomal system and degradation

We are interested in how autophagosomes form, as well as their physiological roles and how autophagy integrates with other lysosomal degradation pathways.

Mechanical stress

We recently discovered that autophagy is dramatically upregulated by mechanical stress. This happens upon  compression of both Dictyostelium and human cells.


 

Figure 2 Mech stress copy

Changes in the physical environment are a universal challenge for cells, but how they respond to these is very poorly understood. The up-regulation of autophagy may provide a way for cells to link physical damage to repair and reprogramming. We are therefore working to understand the role of autophagy in the response to mechanical stress in a number of physiologically relevant cells, as well as the signalling pathways involved.