As it turns out, mitochondria are more than the “powerhouses of the cell,” as they are commonly referred to. These shape-shifting entities also decide whether a cell lives or dies—playing a key role in our overall health and countless diseases.
Scripps Research assistant professor Danielle Grotjahn, PhD, has dedicated her research to better understanding mitochondria, including how they influence everything from cancer to Alzheimer’s disease. By pioneering cutting-edge imaging technologies, Grotjahn and her lab are examining these cellular components in never-before-seen ways. These high-resolution readouts could reveal the different mechanisms that lead to mitochondrial dysfunction and ultimately disease.
Grotjahn sat down for an interview with the Science Changing Life podcast to unpack her research, as well as share the countless reasons why the mitochondria are her favorite cellular organelles.
What is the main role of mitochondria?
If I were on the marketing and rebranding team for mitochondria, I might switch up their catchphrase a little bit. We call mitochondria the “powerhouse of the cell” because they generate energy, but we now appreciate that they do a lot more for the cell than that. Now, people are changing that catchphrase to something like the “stress sensor” or the “signaling hub.” I think I even saw someone call them “the CEO.”
This is because mitochondria are an essential hub for receiving different signaling inputs from the cell. Based on these inputs, they make critical decisions about how the cell should respond. For example, they have a huge role in dictating cell fate—in other words, whether a cell activates pathways to stay alive and keep growing and propagating, or whether a cell initiates programmed cell death, what we call apoptosis. My lab is really interested in understanding how that happens.
How do mitochondria impact health and disease?
This “cell fate” aspect of mitochondria—how they decide if a cell lives or dies—is important for many different types of diseases. For example, there’s neurodegeneration, which is caused by an overactivation of pathways that leads to premature neuronal cell death. On the flip side, you have diseases like cancer, which leads to uncontrolled cell growth.
So, you have these two groups of devastating diseases where on one hand you want to preserve the life of cells, and on the other you want to control the division and that programmed cell death aspect. Mitochondria play a role in both, and we’re trying to understand how their function ultimately leads to these very distinct outcomes.
How is your lab examining mitochondria in a new way?
We’ve found that mitochondria’s ability to respond to different stress signaling pathways has to do with its ability to change shape. My lab is interested in studying the interactions that help them change shape and we are harnessing cutting-edge imaging technologies to do this.
Historically, one thing research has lacked is an ability to look at the very fine details of the mitochondria. It was like looking at a car and seeing it move, but not really understanding its individual parts. Cryo-electron microscopy—one of the imaging technologies my lab is using—enables us to look at the entire car, the entire mitochondria, and all the detailed parts that make up the mitochondria itself. It’s like taking a microscopic CT scan of your sample, and you have a reconstructed representation of what the inside of the cell looks like.
What inspired you to pursue a career in science?
There wasn’t any moment when I was younger that I thought: “I want to be a professor or a scientist.” But my scientific curiosity was always a common aspect of my childhood. And I think for me, the initial curiosity was growing up in Wisconsin and playing outside in the woods. My grandparents had five acres of land with streams and gardens, and I became fascinated with the natural world.
It’s a very cheesy story, but when I was about nine years old, I was gifted a beginner’s microscope kit for my birthday. And I remember thinking it was so cool, like something a real scientist would own. I would take leaves or scrape the inside of my cheek and look at it. It was sort of like unlocking an entire new microscopic world.
Listen to Grotjahn’s full interview on the Science Changing Life podcast.