Mitochondria are ubiquitous organelles that are the primary source of energy for most eukaryotic organisms. Aside from their role in ATP generation, mitochondria are also involved in a host of cellular processes including growth, differentiation, proliferation, and even cell death. Perturbations in mitochondrial function consequently contribute to a number of conditions including cardiovascular disease, cancer, and neurodegeneration. A primary means by which mitochondria influence these pathogenic processes is through the coordinated uptake of cellular calcium and the resultant production of reactive oxygen species.
Recently, we demonstrated that a single calcium transient is sufficient to evoke endothelial inflammation via the activation of NF-kB. However, calcium signals are extremely variable and differ according to the stimulus and cell type. Thus, disparate calcium signaling patterns may uniquely influence mitochondrial calcium uptake and function, especially with regards to production of reactive oxygen species. Regulation of reactive oxygen species generation both spatially and temporally may therefore constitute a primary means by which the mitochondrion can dictate and influence downstream signaling.
To better understand this process, our laboratory combines advanced biomedical imaging and molecular biology techniques with classical biochemical analyses in order to uncover how mitochondria influence divergent calcium signals via reactive oxygen species. We further aim to investigate the mechanism in which mitochondria generate reactive oxygen species, the cellular targets of reactive oxygen species, and how both transient and chronic mitochondrial oxidant production governs cellular function. Ultimately, we hope to delineate how mitochondria integrate external stimuli with cellular metabolism to efficiently couple function with energy production, and then exploit these molecular pathways to address the co-morbidity associated with human diseases.