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Human skin cells with "healthy" mitochondria (light blue): - NLRP10 (yellow-green) is distributed over the entire contents of the cell, apart from the nucleus (blue-violet).
© Image: Kim S. Robinson / Skin Research Institute Singapore

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Loss of mitochondrial integrity induces inflammasome activation

Function of NOD-like receptor NLRP10 revealed

The recognition of pathogens and sterile damage may result in pyroptotic cell death and inflammation. This is brought about by the formation of protein complexes called inflammasomes. ImmunoSensation2 speaker Prof. Eicke Latz and his team at the University of Bonn, together with colleagues from the University of Singapore, now revealed a new function for the inflammasome component NLRP10. The sensor warns of damage to the mitochondria. If it does not function properly, chronic skin diseases can result. The sensor may also be important for unimpaired heart and bowel function. The results have now been published in the journal Nature Immunology.

Every cell in the body has numerous sensors that monitor its function. Some sound the alarm after a virus attack, for instance; others kick in when any kind of damage threatens the cell's survival. "We have now discovered that a molecule called NLRP10 also acts as a sensor," explains Prof. Dr. Eicke Latz, head of the Institute of Innate Immunity at the University Hospital Bonn. "This was completely unknown until now."

The scientists were able to show that NLRP10 detects when the mitochondria in the cell malfunction and lose their integrity. As soon as an NLRP10 sensor detects damage to mitochondria, inflammasome formation is initialized, ultimately causing the cell to perish and be disposed of by summoned immune cells.

Fire alarm prevents long-lasting smoldering fire

"This process is hugely important," explains Latz, who is also a member of the Transdisciplinary Research Area "Life and Health" at the University of Bonn. "Disruption of this mechanism can result in chronic inflammation," the researcher emphasizes. "Killing cells with mitochondrial defects may sound drastic. Ultimately, however, this step prevents more serious consequences."

Not all cells in the body express NLRP10. The sensor occurs primarily in the outermost skin layer, the stratum granulosum. The skin is directly exposed to environmental stimuli such as UV radiation, but also pathogens. This could potentially result in accumulated damage. The mechanism described now ensures that affected cells are effectively disposed of. "If a mutation causes the NLRP10 sensor to malfunction, this can result in a chronic skin inflammation called atopic dermatitis," explains Dr. Tomasz Próchnicki, who performed an important part of the experiments for his doctorate in Latz's research group.

Sensor is also found in the intestinal wall and heart

Large quantities of NLRP10 are also found in the intestinal wall cells. These also have regular contact with pathogens and potentially harmful substances. Another organ in which the sensor can be detected is the heart: It is particularly dependent on a well-functioning energy supply. This may make it especially important to quickly kill and replace cells with defective mitochondria.

The study may potentially also open up new therapeutic perspectives. "It is conceivable to specifically modulate the NLRP10 sensor using certain substances in order to stimulate the formation of inflammasomes," Latz explains. "This approach might enable chronic skin diseases to be better controlled."


In addition to the University Hospital and the University of Bonn, the Skin Research Institute of Singapore, the Technical University of Dresden and the University of Hohenheim were involved in the work. The
study was funded by the German Research Foundation (DFG), by EU funds under the European Union's Horizon 2020 program, by the Helmholtz Association, and by the Nation Research Foundation in Singapore.


Tomasz Próchnicki et al.: Mitochondrial damage activates the NLRP10 inflammasome; Nature Immunology; DOI: 10.1038/s41590-023-01451-y


Prof. Dr. Eicke Latz

Institute of Innate Immunity of the University of Bonn

Co-speaker of the Cluster of Excellence "ImmunoSensation2"

Tel. +49 228 287-51239


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