Mitochondria are well known as energy suppliers, and powerhouses of cells, but they have other crucial functions as well. One of those functions is outcompeting pathogens for resources, according to new findings published in Science. In this study, scientists have shown that mitochondria in cells can starve pathogenic invaders by taking up the available folate (vitamin B9), which can prevent a parasitic infection from getting worse. This work determined that the folate taken up by mitochondria deprived a parasite known as Toxoplasma gondii, making the parasite’s growth slow down.
Toxoplasma gondii is a parasite commonly found in cat feces or undercooked meat. When the parasite spreads to people, it can cause an infection called toxoplasmosis. While it often causes no symptoms, it can be very problematic in pregnancy or in the immunocompromised; the infection can cause growth problems in fetuses.
T. gondii infections cause changes in the brain; they make mice less afraid of cats, and the infection can make humans more tolerant of cat urine smells.
This work has also suggested that vitamin intake might make mitochondria better at fighting some infections, like toxoplasmosis.
“A lot of people think of mitochondria as energy factories, and that pathogens can just exploit the powerhouse by consuming the energy they generate,” said corresponding study author Lena Pernas, a UCLA professor. “But the reality is that mitochondria are actually a kind of domesticated bacteria that compete with invading pathogens for nutrients.”
In this study, the researchers examined human cells that were infected with T. gondii, and found that the amount of mitochondrial DNA had increased during infection. There were also higher levels of a protein called ATF4, which can help regulate gene expression. Cells could sense the infection because of the parasitic proteins that were generated, leading to a response that ramped up mitochondrial metabolism.
“Pathogens have an arsenal of effectors, which are proteins that go into the host cell and perturb cell function. But the host cell was able to say to the mitochondria, ‘Hey, we’re detecting the proteins of this invader. Let’s activate this response,’” Pernas explained.
When ATF4 was genetically eliminated from human cells, the parasites grew more.
The increased metabolic rate of the mitochondria was causing the organelles to consume more folate as well. Since the T. gondii need folate to grow, the lack of folate made their growth slower. These findings may also apply to other infections.
“I think this could apply to any microbe that is dependent on folate to produce that particular nucleotide,” said Pernas. “This would include Plasmodium, which causes malaria, for example. Going forward, we can ask whether folate restriction via mitochondrial metabolism defends against other kinds of infections.”
