Lena Pernas had an early fascination with infectious disease that has expanded to include the role of mitochondria—which she dubs domesticated microbes—as cellular defenders against infection. After first establishing a laboratory at the Max Planck Institute for Biology of Ageing, she recently returned to her undergraduate institution, the University of California, Los Angeles (UCLA), to research the metabolism of infection using Toxoplasma gondii as a model system.
How did you become interested in infectious diseases?
My father was always trying to get my siblings and me curious about something, so he brought home different books and games that would pique our interest. The Oregon Trail had a fun cousin game called The Amazon Trail. The goal was to go down the Amazon River, where different things could happen to each player. I was fascinated that you could get malaria, and then you had to find the Cinchona tree to cure yourself. I also loved the glossary that contained all the infectious diseases that one could contract in the Amazon. That is what started my obsession with parasites.
From an early fascination with infectious diseases to leading her own lab at UCLA, Lena Pernas studies how mitochondria function as cellular defenders against parasitic infection.
Kristen Neumann/AP Images for HHMI
Was that the moment you decided to pursue a career in research?
I knew I loved science and disease, so I wanted to be a doctor. As a kid, I thought that the only way to discover science was through medicine. At UCLA, I decided to study microbiology. Then, a friend of my sister's was in an incredible program called Maximizing Access to Research Careers (MARC). It was an NIH-funded, two-year fellowship for undergraduates that paid awardees to do research. When I learned about scientific research through this program, I thought, this is what I've been looking for. I applied, was accepted, and started working in Kent Hill's laboratory studying trypanosomes, a parasite that causes sleeping sickness. I do not think there was ever another path for me after I learned about research.
What has it been like returning to UCLA as an assistant professor?
It has been amazing. I was initially concerned that I would feel like a child because many of the folks in this department are people that I took classes with as an undergraduate. I felt like there would always be this “I'm still a pupil” mentality, but they have never treated me as such. I have a wonderful community of amazing colleagues that are welcoming, supportive, and collaborative.
Members of the Pernas lab at UCLA study how host metabolism changes to defend against parasites such as Toxoplasma gondii.
Temitope Ademolue, PhD
What sparked your interest in the role of mitochondria during infection?
A lot of my current research started in graduate school with my PhD advisor, John Boothroyd. He showed me electron micrographs of monocytes that had been isolated from mice infected with Toxoplasma gondii. For me, one of the most striking consequences of infection was that the mitochondria surrounded the vacuole that the parasite resided in. I thought this was fascinating and wondered why the mitochondria were doing that. So, I explored the molecular mechanism that binds the parasite vacuole to the mitochondria.1 However, the mitochondria that were attached to a Toxoplasma-containing vacuole were elongated and had a different shape than the mitochondria in uninfected cells. The traditional perspective from a microbiologist was that the parasite is exploiting the mitochondria, but towards the end of my PhD program, I began to think that maybe the host is trying to do something to the parasites using mitochondria. In my postdoctoral fellowship in Luca Scorrano's laboratory, I found that the changes in mitochondrial shape seem to correlate with changes in their metabolism.2 Healthy, elongated mitochondria take up fatty acids, limiting the fatty acids available to the parasites. This was the first hint that maybe there is nutrient competition between the invading parasite and the mitochondria.
What are you studying now?
The concept of nutrient competition between mitochondria and parasites was a foundation for other questions, including work started by an incredible postdoctoral fellow in my laboratory, Tânia Medeiros. Thinking about mitochondria as domesticated microbes, they need a lot of resources from the host cell. What if parasites also need those resources? She was able to discover a response where host cells sense a pathogen and use the integrated stress response pathway to sequester folate in the mitochondria, depriving Toxoplasma gondii of this vitamin, which it needs for its own replication.3 This was another exciting example of how mitochondria and invading pathogens can compete for nutrients. This was also a fun example of how one can use infection as a lens to study mitochondrial metabolism in infection-independent scenarios.
The interview has been condensed and edited for clarity.
- Pernas L, et al. Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PloS Biol. 2014;12(4):e1001845.
- Pernas L, et al. Mitochondria restrict growth of the intracellular parasite Toxoplasma gondii by limiting its uptake of fatty acids. Cell Metab. 2018;27(4):886-897.
- Medeiros TC, et al. Mitochondria protect against an intracellular pathogen by restricting access to folate. Science. 2025;389(6761):eadr6326.
