14. January 2022

Hostile takeover in the cell Hostile takeover in the cell

Research team with participation of the University of Bonn: Pathogens hijack host mitochondria

Mitochondria are known as energy suppliers for our cells, but they also play an important role in the defense against pathogens. They can initiate immune responses, and deprive pathogens of the nutrients they need to grow. A research team led the Max Planck Institute for Biology of Ageing in Cologne has now shown that pathogens can turn off mitochondrial defense mechanisms by hijacking a normal cellular response to stress. Scientists from the University of Bonn were also involved in the study, which was published in the journal Science.

The parasite Toxoplasma gondii (red) causes mitochondria (green) to shed large structures of their "skin" (yellow).
The parasite Toxoplasma gondii (red) causes mitochondria (green) to shed large structures of their "skin" (yellow). © Xianhe Li/Max Planck Institute for Biology of Ageing, 2022
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To survive, pathogens need to acquire nutrients from their host and counter host defenses. One such defense comes from host mitochondria, which can deprive them of nutrients they need and thus restrict their growth. “We wanted to know how else mitochondrial behavior changes when mitochondria and pathogens meet in cells. Because the outer membrane of these organelles is the first point of contact with the pathogens, we took a closer look at it,” explains study leader Dr. Lena Pernas from the Max Planck Institute for Biology of Ageing.

Mitochondria shed their ´skin`

The researchers infected cells with the human parasite Toxoplasma gondii and observed live under the microscope what happens to the outer compartment of mitochondria. "We saw that mitochondria in contact with the parasite started shedding large structures from their outer membrane. This was so puzzling to us. Why would mitochondria shed what is essentially the gateway between them and the rest of the cell?" says Xianhe Li, first author of the study.

Hostile takeover

But how does the parasite get the mitochondria to do it? The research team was able to show that the pathogen has a protein that functionally mimics a host mitochondrial protein. It binds to a receptor on the outer membrane of mitochondria, to gain access to the machinery that ensures proteins are transported inside the mitochondria. “In doing so, the parasite hijacks a normal host response to mitochondrial stress that, in the context of infection, effectively disarms the mitochondria," Pernas said.

In a cooperation at the Collaborative Research Center 1218 “Mitochondrial regulation of cellular function”, Prof. Dr. Thomas Becker and Dr. Fabian den Brave from the Institute of Biochemistry and Molecular Biology at the University of Bonn investigated the impact of the parasite protein on protein uptake into mitochondria. “Using baker´s yeast as model organism, we found that binding of the parasite protein to the receptor impairs protein import into mitochondria,” said Thomas Becker, member of the Transdisciplinary Research Area “Life and Health” of the University Bonn.

"Other researchers have shown that a SARS-CoV-2 virus protein also binds to this transport receptor. This suggests the receptor plays an important role in the host-pathogen interaction. But further investigation is needed to better understand its role during different infections", said Pernas.

Video about the study


Xianhe Li, Julian Straub, Tânia Catarina Medeiros, Chahat Mehra, Fabian den Brave, Esra Peker, Ilian Atanassov, Katharina Stillger, Jonas Benjamin Michaelis, Emma Burbridge, Colin Adrain, Christian Münch, Jan Riemer, Thomas Becker, Lena F. Pernas: Mitochondria shed their outer membrane in response to infection-induced stress. Science; DOI: 10.1126/science.abi4343

Prof. Dr. Thomas Becker
Institute of Biochemistry and Molecular Biology
University of Bonn
Phone: +49 228 73-2412
Email: thbecker@uni-bonn.de

Corresponding author:
Dr. Lena Pernas
Max Planck Institute for Biology of Aging, Cologne
Phone: +49 (0)221 379 70 770
Email: LPernas@age.mpg.de

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