Intracellular sensor warns of damage to mitochondria

A research team led by the University of Bonn has discovered a so-called intracellular ‘smoke detector’ that warns of damage to the mitochondria — the microscopic power plants that supply the cell with energy. Their results have 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. Prof Dr Eicke Latz, Head of the Institute of Innate Immunity at the University Hospital Bonn, revealed, “We have now discovered that a molecule called NLRP10 also acts as a sensor; this was completely unknown until now.”

Figuratively speaking, NLRP10 detects when the mitochondria in the cell start to smoke due to some malfunction. As soon as an NLRP10 sensor detects damage to mitochondria, it sets off a complicated process. This creates a so-called inflammasome, a complex molecular machine. Its activity ultimately causes the cell to perish and be disposed of by summoned immune cells.

“This process is hugely important,” Latz said. This is because the inflammasome ensures that the fire is stamped out straight away, which prevents a prolonged smouldering fire that would damage other parts of the tissue.

“Disruption of this mechanism can result in chronic inflammation,” Latz continued. “Killing cells with mitochondrial defects may sound drastic. Ultimately, however, this step prevents more serious consequences.”

Not all cells in the body have an NLRP10 sensor. The ‘fire detector’ 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 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,” said Dr Tomasz Próchnicki, who performed part of the team’s experiments.

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, with Latz saying, “It is conceivable to specifically modulate the NLRP10 sensor using certain substances in order to stimulate the formation of inflammasomes. This approach might enable chronic skin diseases to be better controlled.”

Image caption: Human skin cells with ‘healthy’ mitochondria (light blue): The NLRP10 ‘smoke detector’ (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.