Cytoprotection by metacaspases: molecular mechanisms and biological implications

All organisms have specialized proteins that can either kill the cells or grant them survival under stress.

Surprisingly, proteins originally known as dedicated cell killers may, depending on vaguely understood factors, play pro-survival role.

This paradigm shift has dramatically changed our view of caspases: from the major executioners of apoptotic death in 1990s to multifunctional proteins participating in various pathways, including those crucial for cell viability, today.

However, caspases are found mostly in animals and are thought to have evolved from metacaspases (MCAs), widespread throughout all other kingdoms of life, yet remaining poorly understood.

Our recent research suggests that besides executing cell death, MCAs can bestow cytoprotection, in particular under heat stress, by acting as parts of mesoscale molecular assemblies.

Here, we will explore these assemblies: one localized on the cell membrane in a unicellular alga Chlamydomonas and another dispersed through the cytoplasm in Arabidopsis plant.

We will first identify protein components of the cell membrane-associated assembly and MCA substrates cleaved within the cytoplasmic counterparts.

This will facilitate unravelling the structure and physical properties of both assemblies, either purified or within the cells, using cryo-EM and other advanced techniques.

Finally, we will study the role of individual protein components in the formation of these assemblies and in the organismal fitness by genetic methods.