In the Shadel Lab, we study mitochondria, essential organelles inside most cells. Mitochondria are known as the “powerhouses of the cell” because of their key role in generating the high-energy molecule ATP to power virtually all processes in an organism. However, mitochondria do much more than oxidative phosphorylation (OXPHOS) to produce ATP. For example, they are the sites of dozens of other essential biochemical reactions (e.g. heme and iron-sulfur cluster synthesis) and can initiate apoptotic cell death. Mitochondria are also constantly fusing, dividing and moving throughout the cell. Thus, their morphology, motility and dynamics regulate their function. Lastly, mitochondria contain DNA (mtDNA) that is maternally inherited in mammals, usually present at thousands of copies/cell, and, because it encodes thirteen essential subunits of the OXPHOS complexes, causes human diseases and contributes to aging when mutated.
Given the multi-faceted roles of mitochondria, the overarching hypothesis in the Shadel lab is that these amazing organelles are involved in many more processes and pathways than originally thought. Furthermore, we believe they communicate with other organelles within the same cell, and elicit direct intracellular, intercellular, and even peripheral signaling events. Thus, a major emphasize of our work is to understand the nature of these mitochondrial stress-signaling pathways. In doing so, we continue to elucidate novel ways that mitochondria and mtDNA contribute to human diseases, aging and immunity.