Vamsi Mootha: Taking an inventory of mitochondria

Mitochondria, the energy reactors of the cell, are estimated to contain approximately 1,500 proteins, but the mito-chondrial genome itself only encodes about 13 of them. The remaining proteins are immigrants that are encoded by the nuclear genome. Vamsi Mootha is using an integrative genomics approach to identify all of these proteins and their functions and to understand how their mutated versions lead to disease. Mootha, who built thermodynamic models of mito-chondrial function as a medical student (1), honed his genetics skills during his years as a medical resident and a postdoc (2–5). In addition to expanding the database of mitochondrial proteins and networks, Mootha, now an assistant professor at the Broad Institute in Cambridge, MA, is also trying to figure out why mitochondria are often the source of drug toxicity (6). His team has found that many commonly used drugs suppress mitochon-drial gene expression or interrupt the cross-talk between the mitochondrial and nuclear genomes. Their discoveries help explain many physiological mysteries , such as why cholesterol-lowering statins cause muscle cramps in some users—because they increase the production of mitochondrial toxic byprod-ucts and lower the cell's energy. Mootha, who was awarded the MacArthur Foundation's Genius grant in 2004, discussed his ventures into mitochon-dria in a recent interview. How did you get interested in science? I come from a family of physicians. My father is a general surgeon and my three siblings and their spouses are all physicians. So as a child, I wanted to be a physician as well. But, in my teens, I became enamored by math and computer science. I was actually a math geek in high school who competed in various math contests. You pursued your interest in math in college. Why did you pick Stanford? I got into colleges on the East and West coasts, and in Texas, which is where I grew up. But, being an avid tennis player in high school, the weather in Northern California and the popularity of tennis there made Stanford really appealing to me. That, and the fact that math and computer science are so strong at Stan-ford, drew me there. Did you end up playing tennis for Stanford too? If I could play tennis for Stanford, I wouldn't be talking to you right now. I'd be on ESPN. Fair enough. So how did you go from being a mathalete to becoming a med student? I took a biology class during …