Scientists at the University of Freiburg‘s Faculty of Medicine discovered that when energy production in mitochondria suddenly stops, it prevents normal cell death (apoptosis) and instead triggers an inflammatory response.
This finding highlights mitochondria’s important role in determining whether cells survive or die under stress. It suggests that mitochondria not only produce energy but also influence inflammation.
Prof. Dr Olaf Groß, head of the study, a scientist at the Institute of Neuropathology at the Medical Center – University of Freiburg and a member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg said, “We found that mitochondria provide a kind of decision-making aid: they regulate whether a cell undergoes clean, silent apoptosis or releases pro-inflammatory messenger substances.”
“This finding helps us better understand how the body balances cell protection and defense mechanisms. This could open up new avenues for the treatment of inflammatory diseases.”
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When ATP levels in mitochondria drop significantly, cytochrome c, a protein essential for apoptosis, stays trapped inside the mitochondria, preventing the cell from dying despite external death signals. Instead of apoptosis, the mitochondria activate mechanisms that trigger an inflammatory response, alerting the tissue to potential threats.
Researchers have found that a cellular “sensor” called NLRP3 is activated when mitochondria stop energy production. However, a second signal from other cell parts is required to activate the NLRP3 sensor fully. This “two-signal mechanism” ensures inflammation is only triggered in response to serious threats, protecting healthy cells and preventing unnecessary inflammation that could harm tissue.
Prof Groß said, “This discovery could help treat diseases in which inflammatory processes play a role – such as gout, type 2 diabetes or severe cases of COVID-19.”
“In the future, drugs could be specifically designed to mitochondria or the activation of NLRP3 to control inflammation better and, on the one hand, to prevent damage to healthy tissue and, on the other, to promote the immune response to infection or the rejection of cancer by the immune system.”
Journal Reference:
- Benedikt S. Saller, Svenja Wöhrle, Larissa Fischer et al. Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation. Immunity, 2024; DOI: 10.1016/j.immuni.2024.10.012
