Projects
Tissue-specific mitochondrial physiology
Often simplified to “powerhouses of the cell," mitochondria are complex organelles with various forms and functions across mammalian tissues. How mitochondria achieve this tissue specialization is not well understood. We combine mass spectrometry-based profiling, genetics, and mammalian physiology to understand how mitochondria maintain tissue specific functions, and how perturbing mitochondrial function across different tissues elicits distinct pathology.
Mechanisms of mitochondrial biogenesis and turnover
Of the 1158 proteins in mammalian mitochondria, only 13 are synthesized within the organelle. The remaining 99.7% must be translated, targeted, transported, sorted, processed, and refolded within a specific compartment within the mitochondrion. Further, many cellular mechanisms of protein turnover, such as the ubiquitin-proteasome system, are not physically accessible to many mitochondrial proteins due to their sequestration within mitochondrial membranes. We are interested in how cells generate functional mitochondrial proteins, as well as how these proteins are turned over in normal and pathological states.
The uncharted mitochondrial phosphoproteome
Phosphorylation has long been associated with mitochondrial metabolism, discovered on pyruvate dehydrogenase over 50 years ago. Recent advances in phosphoproteomics have shown that over 91% of the mitochondrial proteome has at least one experimentally determined phosphoisoform. Our recent work shows that disrupting mitochondrial-resident phosphatases can have devastating consequences, suggesting proper management of mitochondrial phosphorylation is critical in mammals. We are working to understand what these modifications do, how they come about, and the full spectrum of pathology arising from their dysregulation.