Capturing the moment a cell shuts the door on free radicals

The moment a cell shuts the door on free radicals.
Illustration Credit: Catrin Jakobsson, Lund University

For the first time, researchers have been able to show how a cell closes the door to free radicals – small oxygen molecules that are sometimes needed, but that can also damage our cells. The study is published in Nature Communications and was led by Lund University. 

For our cells to function, they need to maintain a careful balance between beneficial and harmful oxygen molecules known as free radicals. One of the most important is hydrogen peroxide – the same substance found in disinfectants, but which our cells use in very small amounts to send important signals. However, in excessive concentrations, hydrogen peroxide can cause damage and even cell death.  

“Our cells produce free radicals when we inhale oxygen. Previously, it was thought that the hydrogen peroxide from oxygen could flow freely through ‘doors’ of the cell membrane, i.e. channels that also flux water, but we have shown that the channels in the cell membrane appear to have a protective system,” says Karin Lindkvist, who led the study and is a professor at Lund University. 

We were surprised by what we saw. It was like witnessing, in the moment, the cell closing the channel on something that could otherwise cause it harm. Doing that acts as an automatic protection against dangerous levels entering the cell. 

Thanks to advances in cryo-electron microscopy, the researchers were able to see that the door is normally open, allowing molecules such as hydrogen peroxide, water, and glycerol to enter. However, if the amount of hydrogen peroxide outside the cell is too high, hydrogen peroxide molecules get stuck on the outside of the channel. These then act as a “lock” holding the door closed and protecting the cells from damage. 

The cryo-electron microscopy showed the channel closed upon hydrogen peroxide – something no one has shown before.  

The discovery provides new understanding of how cells protect themselves against stress and damage and how they regulate free radicals – knowledge that may help researchers to understand diabetes, cancer and other conditions in which cells’ stress levels are disturbed.  

“Cancer cells, for example, produce extreme quantities of free radicals when they grow quickly. Despite this, they do not die as a result, which suggests that they have ways of getting rid of the excess. One possibility is that they use the same type of channel in the cell membrane to expel the surplus and avoid being suffocated by their own free radicals. In our next study, we want to investigate whether it is possible to kill cancer cells by blocking the channels,” says Karin Lindkvist. 

Funding: The Swedish Research Council, the Swedish Diabetes Fund, the Swedish Cancer Society

Published in journal: Nature Communications

Title: Structural insights into AQP3 channel closure upon pH and redox changes reveal an autoregulatory molecular mechanism

Authors: Peng Huang, Raminta Venskutonytė, Carter J. Wilson, Sara Bsharat, Rashmi B. Prasad, Pontus Gourdon, Isabella Artner, Bert L. de Groot, and Karin Lindkvist-Petersson

Source/Credit: Lund University | Tove Smeds

Reference Number: bchem122225_01

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