Mitochondria defend cells against infections

Nutrient competition restricts parasite growth

To the point

• Nutrient Competition: Cellular powerhouses restrict pathogen growth by outcompeting them for vital resources.
• Metabolic Adjustments: Host cells adapt to infections by rewiring metabolic processes within mitochondria.
• Broader Impact: Insights into these cellular defenses could pave the way for new strategies to combat chronic infections.

Chronic infections impact a substantial portion of the global population, presenting ongoing challenges to healthcare systems and compromising patient well-being. Researchers at the Max Planck Institute for Biology of Ageing have discovered a surprising ally in the fight against infection: the cell’s own mitochondria. Best known as the cell’s powerhouses, mitochondria also play a defensive role by competing with pathogens for vital nutrients. During infection, mitochondria enter a metabolic tug-of-war with intracellular parasites, like Toxoplasma gondii, battling for access to folate, thereby inhibiting pathogen growth. This discovery highlights a unique defensive strategy employed by host cells and opens up new possibilities for developing therapies against folate-dependent pathogens, such as Toxoplasma and Plasmodium, which cause toxoplasmosis and malaria respectively.

During infection with the human parasite Toxoplasma gondii, researchers observed the activation of the integrated stress response, which rewires mitochondrial metabolism.  

This response enhanced mitochondrial activity, leading to increased demand for folate. a critical nutrient for nucleotide synthesis. Consequently, mitochondria limit the parasite’s access to folate, curtailing its growth and proliferation. Mice unable to activate this stress response showed faster parasite growth, confirming the pathway’s protective role in vivo.

"Mitochondria and intracellular pathogens compete for the same nutrient resources. However, we previously did not know whether cell’s leverage mitochondria to defend against invading pathogens like Toxoplasma”, explains Tania Medeiros, first author of the study.

In forthcoming steps, researchers aim to unravel the precise mechanisms triggering the stress response during infection and identify the implicated proteins. They are also eager to explore the feasibility of enhancing mitochondrial activity to combat infections. “Boosting mitochondrial metabolism could potentially defend against folate-dependent pathogens like Plasmodium or Toxoplasma. This opens the door to novel therapeutic possibilities," adds Lena Pernas, the study's lead author.