Cells must tidy up their proteins to cope with stress

Breaking new ground 23. nov 2020 3 min Professor Morten Petersen Written by Kristian Sjøgren

When cells adapt their genetic expression to cope with climate change or threats from bacteria, they first have to remove superfluous or damaged proteins. Otherwise, things can go completely haywire.

All the cells in your body – or in a beech, poppy or ostrich – can adapt to the environment by adjusting their genetic expression and turning on or off thousands of genes and genetic signalling pathways.

People, beeches, poppies and ostriches do this when they are exposed to stress factors such as heat or cold, threats from bacteria, chemical stress or anything else that can threaten the cells and thus the whole organism.

New Danish research now shows that before the cells can benefit from activating the genetic stress response, they must first use autophagy to tidy up all superfluous or damaged proteins so they do not interfere with the many complex signalling pathways involved that need to function smoothly.

The research has been published in the EMBO Journal.

“This process has not been studied much previously, but we show that it is probably an essential and universal mechanism, and this knowledge helps us to understand how cells adapt to the environment. Regardless of which processes the cells initiate, superfluous or damaged proteins from the previous processes must be tidied up to avoid major errors in the new processes,” explains Morten Petersen, Professor, Department of Biology, University of Copenhagen.

Various situations require cells to adapt to new environments

The research examined how cells establish a temporary state or a new identity in their genetic expression.

Cells may need to reprogramme their state at various times. For example, a cell has to adapt to the surroundings getting warmer. A cell in a poppy growing in a field on a sunny spring day will need to adapt to tolerate heat as summer approaches.

Cells may also need to change identity from being differentiated as one specific type of cell to becoming a stem cell. This dedifferentiation enables a cell to redifferentiate into other types of cells, organs and even whole organisms in plants.

“This process is especially interesting for pharmaceutical purposes and in many other health contexts. Inducing diseased cells to dedifferentiate to stem cells and start over can potentially cure many diseases caused by defective cells. Understanding what is needed for cells to change identity therefore provides many interesting perspectives,” says Morten Petersen.

Cells tidy up when organisms change their identity

When a cell needs to switch state or identity, the first step is to remove the proteins that define its current state or identity through autophagy.

The poppy may have adapted to cope with frosty nights in early April. Then it has to switch state to cope with hot summer days.

The poppy has many proteins required to cope with cold and needs to remove them to make room for proteins that can tolerate heat.

“How cells adapt genetically and epigenetically has been comprehensively studied, but there have been very few studies of what the cells do with all the proteins that need to be tidied up to enable the cell to reprogramme itself. Simply silencing the genes is not enough,” explains Morten Petersen.

Autophagy – a unique mechanism for tidying up proteins

Morten Petersen’s research shows that autophagy is necessary for cells to switch state in response to external stress.

Cells use autophagy to clear out everything that they no longer need – including whole organelles inside the cells and proteins.

In experiments with cells of Arabidopsis thaliana (thale cress), Morten Petersen disarmed the autophagy by impairing the relevant genes. This totally eliminated the cells’ ability to adapt to changes in the environment.

The cells have difficulty differentiating and cannot switch state in response to extracellular stress.

Morten Petersen also examined what happens to cells that dedifferentiate into stem cells and then redifferentiate into a new state.

“The stem cells that lack autophagy also have great difficulty in restarting the redifferentiation programmes. However, when they eventually re-start, the cells need autophagy to control cellular reprogramming intensity. Thus, autophagy-deficient cells go completely haywire and launch a snowball effect,” says Morten Petersen.

The resulting failure of the process of tidying up in Morten Petersen’s experiments also produced considerably weakened plants, which adapted poorly when the surroundings changed slightly.

Learning more about the underlying mechanisms

Morten Petersen says that, although researchers now know much more about a general mechanism in all animal and plant cells on Earth, there is still much that they do not understand, which will be the subject of future research.

The researchers will delve deeper into understanding the mechanisms involved when autophagy is initiated to tidy up superfluous and damaged proteins between identities.

“Understanding how these processes occur is invaluable, because they play a role in everything from maintaining the health of a cell to how people adapt to the environment. These processes are therefore not merely relevant for understanding many diseases but also for understanding how we function biologically,” says Morten Petersen.

Autophagy mediates temporary reprogramming and dedifferentiation in plant somatic cells” has been published in the EMBO Journal. In 2017, the Novo Nordisk Foundation awarded a grant to Morten Petersen for the project Global Increase in Plant Performance Using Natural, Bioactive Compounds.

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