A cell is shown in a picture. Credit: Gary Mo.
A study published by researchers at the University of Illinois Chicago shows that the process of cell death caused by infections can be halted, even though it has been thought to be irreversible once initiated.
The discovery means that scientists have a new way to study diseases that are related to malfunctioning cell death processes, like some cancers, and infections that can be complicated by out-of-control inflammation caused by the process. Acute respiratory distress syndrome is one of the major causes of COVID-19 illness.
A series of biochemical reactions that use gasdermin, a protein, to open large pores in the cell, is called pyroptosis. To understand more about this process, the UIC researchers designed an "optogenetic" gasdermin.
The cell death process plays an important role in the body, in both healthy states and unhealthy ones, but studying it has been challenging.
Mo said that it's difficult to control the mechanisms that play in live cells because they are initiated by unpredictable pathogens, which in turn have different effects on different cells and people.
Mo said that the optogenetic gasdermin allowed them to skip over the unpredictable pathogen behavior and the variable cellular response because it mimics at the molecular level what happens in the cell once pyroptosis is initiated.
The researchers used this tool to precisely activated gasdermin in cell experiments and to observe the pores under different circumstances. They discovered that certain conditions, like specific concentrations of calcium ion, caused the pores to close in a short time.
This automatic response to external circumstances shows that pyroptosis self-regulates.
This showed us that this form of cell death is not a one-way ticket. Mo said that the process was programmed with a cancel button. Understanding how to control this process unlocks new avenues for drug discovery, and now we can find drugs that work for both sides, where we could previously only remove this important process.
The co-authors of the Nature Communications paper are Ana Santa Cruz, Kevin Schnur, and Asrar Malik.
The Gasdermin D pores are regulated by local phosphoinositide circuitry. There is a DOI titled " 10.1038/s41467-021-27692-9".
Nature Communications is a journal.
Scientists uncover new information about the cellular death process, which was thought to be irreversible.
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