Whether cells in the human body survive or die under stress depends, among other things, on their mitochondria. Scientists from the Faculty of Medicine at the University of Freiburg have shown that a sudden stop of energy production in these cellular “power plants” prevents normal cell death or so-called apoptosis and instead triggers an inflammatory response. The results of this research were published in the journal Immunity on November 20, 2024.
“We found that mitochondria provide a kind of decision-making aid: They regulate whether a cell undergoes clean, silent apoptosis or whether it releases pro-inflammatory messenger substances,” explains Professor Dr. Olaf Groß, head of the study and scientist at the Institute. of Neuropathology at the University Medical Center of Freiburg and member of the CIBSS Cluster of Excellence of the Center for Integrative Studies of Biological Signaling at the University of Freiburg. “This finding helps us better understand how the body maintains a balance between cellular protection and defense mechanisms. This could open new avenues for the treatment of inflammatory diseases.” The research work was funded as part of several collaborative research centers at the University of Freiburg.
A complex interaction for good health
The universal “fuel source” for cellular activity is ATP (adenosine triphosphate). If ATP in the mitochondria drops sharply, a protein important for apoptosis, known as cytochrome c, becomes trapped in the mitochondria and the cell does not die, even if it receives the signal to do so from the outside. Instead, mitochondria activate mechanisms that trigger an inflammatory response, which puts the tissue on alert and prepares it for a possible threat.
Researchers have now discovered that a special “sensor” in cells, known as NLRP3, is activated when mitochondria stop producing energy. However, a second signal from other areas of the cell is needed to activate the NLRP3 sensor. This so-called “two-signal mechanism” ensures that inflammation is only activated in the event of serious danger, thus protecting healthy cells. This allows the body to react to threats in a targeted way while preventing unnecessary inflammation that could damage tissue.
New options to treat inflammatory diseases
This discovery could be useful for the treatment of diseases in which inflammatory processes play a role, such as gout, type 2 diabetes or severe cases of COVID-19. “In the future, specific drugs could be designed for mitochondria or NLRP3 activation in order to better control inflammation and, on the one hand, prevent damage to healthy tissue and, on the other, promote the immune response to infections or the rejection of cancer by the immune system,” says Groß.