A discovery reported on Nature Communications will give to scientists a new way to study diseases related to an erroneous cell death process called pyrotosis.
The discovery will go a long way in understanding some cancers and infections complicated by out-of-control inflammation caused by these processes. Infections such as sepsis, for example, or acute respiratory distress syndrome, among the main complications of COVID-19.
Eyes on pyrotosis
Pyrosis is a series of biochemical reactions that use gasdermin, a protein, to open enlarged pores in the cell membrane and destabilize the cell. To better understand this process, researchers from the University of Illinois Chicago (UIC) designed an "optogenetic" gasdermin that was genetically engineered to respond to light.
"The cell death process plays an important role in the body, in both healthy and unhealthy states, but the study of pyrotosis, which is an important type of cell death, has been challenging," he says. Gary Mo, assistant professor of the UIC in the department of pharmacology and regenerative medicine.
The pirotosi tape can be rewound
Mo believes that methods of examining the pyrotoxic mechanisms at play in living cells are difficult to control because they are initiated by unpredictable pathogens, which produce different effects in different people (and cells).
"Our gasdermina optogenetics it allowed us to ignore these variables, because it mimics at the molecular level what happens in the cell once pyrotosis starts, "Mo said.
Researchers applied this tool and used fluorescent imaging technology to precisely activate gasdermin in cellular experiments. They found that if there are specific concentrations of calcium ions, cell pores close within tens of seconds. This form of cell death is not a one way ticket.
Will we understand how to control this form of cell death?
"This study showed us that this process has a cancel button, an off switch," Mo said. "Understanding how to control this process opens up new avenues for drug discovery that will allow us to remove pyrotosis."
The implications? Too many to imagine at the moment, but this is a small big step forward in the study of ways to extend life and health.