The V-ATPase protein V1H was found to be involved in the alarm process.
Scientists at the Francis Crick Institute have revealed how cells ‘sound the alarm’ when they are damaged or infected by bacteria or viruses, causing acid to leak from cellular compartments – a finding that could aid in the development of new drugs.
This study Molecular and Cellular It turns out that a protein called V1H, which incorporates the machinery needed for autophagy (breaking down parts of the cell), is involved in this process.
Cells in the body need acidic compartments to digest and recycle nutrients, and that acid is pumped into them by a group of proteins called V-ATPases, or “proton pumps.” When cells become damaged or infected, acid leaks out of these compartments, and cells need to be able to detect this.
A new study reveals how cells detect acid leaks and how the V-ATPase complex can sound the alarm if the system malfunctions.
The researchers used special techniques to determine the structure of the pump and discovered that V1H of the V-ATPase complex is involved in the alarm process.
“We found that this damage-sensing role of V-ATPase is active in many contexts, including during viral infection and after activation of certain immune receptors,” said lead author Luis Timimi, a student in the Crick Institute’s Laboratory of Infection and Cell Biology.
Additionally, the team found that neurons develop a shorter form of V1H, but this fails to signal to autophagy proteins that the compartment has lost its acidity. Instead, the researchers speculate that this shorter form of V1H allows autophagy proteins to carry out their specialized functions without sounding the alarm unnecessarily.
Timimi added: “By identifying the subunits of V-ATPase involved in this function, we were able to show how the state of V-ATPase controls these damage responses.”
The team also believes that some microbes, such as Salmonella, are able to evade detection by antagonizing proton pumps.
This suggests that targeting this pathway may provide a valuable new avenue for drug development.
