Here is the full transcript of Lena Pernas’ talk titled “How Mitochondria May Protect Us Fom Disease” at TEDxPadova 2023 conference.
Listen to the audio version here:
TRANSCRIPT:
The Trillions of Microbes in Our Bodies
There are trillions of microbes in this auditorium. Many of them are the bacteria that live on and in our bodies. The vast majority of these microbes, however, are the ones that live in almost each and every one of our cells. The microbes that I’m referring to are mitochondria.
For those of you who remember your high school textbooks, you’re probably thinking, “Wait a minute, mitochondria are not microbes, they’re small things that perform important functions in our cells.” You’re absolutely right. But today I want to share with you why we should instead think of mitochondria as microbes and how viewing them from this microbial lens can help us discover new ways to combat infectious disease.
The Bacterial Ancestry of Mitochondria
Mitochondria have a dirty little secret. Their ancestors were bacteria. Although the idea that mitochondria were derived from bacteria was considered ridiculous when it was first proposed in the 1960s, we now understand that about 1.5 billion years ago, a bacterium found its way into a larger cell and stayed. Thanks to this event, we now have mitochondria, which have retained some of their bacterial traits, traits that render them susceptible to the antibiotics that we all take, and traits like their DNA.
Given that Mother’s Day is approaching, I have to remind you all that all of our mitochondrial DNA comes from our mother. Sorry, Papa. 1.5 billion years later, we cannot live without our mitochondria. If our mitochondria are not happy, we are not healthy. There’s an avalanche of studies that shows that unhealthy mitochondria are linked to all sorts of illnesses, including neurodegenerative, cardiac diseases, and age-related diseases.
The Vital Functions of Mitochondria
So what makes mitochondria so important? Well, we know they perform several important functions. For example, they help us produce hormones like testosterone, estrogen, and cortisol, hormones that help our bodies develop and respond to stress. But probably their most vital function is that they are the powerhouses of our cells.
They produce the chemical energy that is required for life, known as ATP. Your mitochondria are making about 65 kilos of ATP per day that helps power your bodies. To do so, mitochondria use about 90% of the oxygen that we breathe and the nutrients that we consume, the same nutrients that are pilfered and consumed by bacteria, viruses, and parasites when they invade our cells.
Mitochondria’s Response to Microbial Invaders
This brings me to the question that has fascinated me for over 10 years. How do our mitochondria respond when there’s another microbe in their territory? Just imagine the scene. Mitochondria are in peace in their cell, making ATP, and then all of a sudden, out of the blue, there’s an intruder.
An intruder who’s making a mess in their cellular home and who’s competing for the same nutrients. You might think I’m about to tell you about how mitochondria seek and destroy these intruders, but the reality is we actually know very little about what mitochondria do to microbial invaders. And that’s because our mitochondria, which have the power of life and death over our cells, are considered to be simply targets during infection.
This is surprising, no? Maybe this makes sense if we only consider mitochondria as powerhouses. Invading microbes could steal their ATP or energy or prevent them from making energy to power cellular defenses. But if we think of them as intracellular bacteria guarding their home, the idea that they don’t do anything in the event of an intruder doesn’t make much sense.
Investigating Mitochondria’s Defense Mechanisms
So in my lab, we try and understand how mitochondria can defend us against microbial invaders. We think that the answers to this question can help us discover new ways to combat microbes. In order to tackle this question, we ask how and why mitochondria change their behavior during infection.
And as our mitochondrial challenger, we use the human parasite Toxoplasma gondii. This parasite infects about one-third of the human population, so that’s about 500 of us in this room. You may have heard of Toxoplasma in the same sentence as cats or poop, and that’s because cats are the definitive host for this parasite.
If a cat is infected, it can pass billions of parasites in its feces, which makes its way to us through contaminated food or the undercooked meat of animals that have been previously infected. So what do mitochondria do when Toxoplasma enters their cell? What I’m showing you here is a video that captures the encounter between parasite and mitochondria.
Toxoplasma, in red, invades a cell full of mitochondria, in green. Mitochondria surround this first parasite and seem to destroy it. What we found is that some of the changes in mitochondrial behavior are linked to changes in their metabolism or mode of eating, because during infection we have a sort of hunger game scenario.
The Hunger Games: Mitochondria vs. Parasites
Both mitochondria and parasite need fats. However, our mitochondria begin to take up more fats, thereby diminishing the parasite’s access to the fats it needs to grow. If we enhance the ability of mitochondria to take up fats, the parasites take up less and grow slower. If we, however, block the ability of mitochondria to use fats, parasites take up more and grow faster.
So this tells us that mitochondria are not simply targets during infection, but can defend our cells against microbes. Considering mitochondria as intracellular microbes guarding their home changes our fundamental perception of our cellular powerhouses and allows us to ask new and powerful questions like, “Can we use what we’ve learned about these hunger games to develop novel antimicrobials?” “Can mitochondria deprive microbes from other nutrients?” “Are there other ways that mitochondria can defend ourselves from microbes apart from these hunger games?”
A Philosophical Question: Are Mitochondria Still Microbes?
We hope to have the answers to these questions in the coming years, but in the meantime I’ll leave you with a take-home message and a question.