What’s the link between mitochondria and cancer?
Cancer cells undergo a big metabolic switch, and that metabolic switch manifests as they grow and divide more rapidly and form tumors. Many start to undergo more glycolysis and less respiration. The mitochondria, because they are the sites of respiration, come into play during the rewiring of metabolic networks. Scientists are looking for a readout of these changes in metabolism related to mitochondria.
How did you become interested in mitochondria?
I’m interested in cell organization. I am really fascinated by how cells count and measure and generate the shape of their structures and how the structure relates to function. [Mitochondria] have such a fascinating shape. I was mesmerized by the beauty of what mitochondrial networks look like, rather than being the small kidney beans you see through EM… I thought they would make a good model for studying the processes of intercellular geometry. This relates to cancer because cell disorganization is a hallmark of cancer. Pathologists use disorganization of the cell as a marker of the progression of the disease.
You study yeast mitochondria, are they very different from mammalian mitochondria?
The main model in my lab has been yeast mitochondria, but we’re starting to look at mammalian mitochondria as well. The reason I picked yeast as a model is that I wanted to study mitochondria in a systems biology way in a cell together with other organelles. Yeast cells were the best place to [study mitochondria] in a quantitative way. You can see the entire mitochondrial network, because the cells are small. Yeast cells can also survive with different levels of mitochondrial function, unlike normal mammalian cells. Yeast cells don’t become cancerous, but when yeast cells grow in colonies, within the colonies you’ll have different subpopulations exhibiting different types of metabolism. This includes more glycolytic versus respiratory cells, similar to what happens in a tumor. And the underlying rules that govern mitochondria in yeast and mammals are the same. They move around on the cytoskeleton, and by Brownian motion, and their mitochondrial morphology relates to cell function… At the clinical health level, the specific molecular differences are important, but for understanding the basic rules, the types of building blocks are the same.
What inspired you to become a scientist?
Everyone in my family is a theoretical physicist, except my brother is an astronomer. My mother finished her PhD when I was 7. I watched how engrossed she was in everything she was doing and I finally asked her, “What are you doing that’s so important that you’re not paying attention to us?” She said “Research, which is when you discover things you don’t know.” I was dumbfounded that we have all these books in the library and there is still stuff we don’t know. I thought, “I have to be part of that.”… I am fascinated by the underlying concept that molecules can self-organize into a functioning cell.
You’re starting a new position at the Allen Institute for Cell Science?
I have been given the amazing opportunity to be one of the directors of the new Allen Institute for Cell Science, whose goal is to generate integrative predictive models of the cell. The whole institute goal aligns greatly with my own personal research goals. So I feel incredibly privileged and humbled and honored to be allowed to be a part of it.
Are you looking forward to the upcoming meeting in San Diego?
I’ve gone to every single ASCB meeting since 2000. It is my meeting. It is my thing. I’m excited to get to participate in it more.
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