Organelle Homeostasis and Aging
Organelles provide important compartmentalization of diverse cellular processes such as DNA replication, metabolite synthesis and storage, and proteolytic degradation. The division of cellular activities into distinct compartments necessitates intricate pathways of organelle crosstalk and quality control that are essential for cells to maintain organelle homeostasis in various environments. It has become increasingly clear that failure to maintain organelle integrity is a hallmark of the aging process across species, and serves as the underlying molecular basis for a number of age-associated diseases including Parkinson’s, Alzheimer’s, diabetes, and lysosomal storage disorders. However, our current understanding of the relationship between aging and organelle biology is limited.
My lab seeks to develop a broad understanding of the mechanisms cells use to achieve organelle homeostasis, and how failure to maintain organelle integrity contributes to aging and the development of age-associated diseases. More specifically, we are working to identify and characterize new pathways of organelle crosstalk and quality control, and determine how aging and metabolic state impact organelle function and integrity. To do this, we are using a budding yeast model system of aging that allows us to systematically analyze organelle structure and function in the context of an aging organism. With this approach, we have uncovered several new pathways of organelle crosstalk and quality control that are critical to the health of aging cells. Two of the pathways we are currently working on include a new metabolic connection between the lysosome and mitochondria that regulates the aging process, and an autophagy-dependent quality control pathway that remodels the mitochondrial proteome in response to changes in the nutrient environment of aging cells. Ultimately, we hope that investigating these pathways as well as others we have uncovered will provide fundamental insights into how organelles communicate within cells, and will open new therapeutic avenues for tackling age-associated diseases that arise from alterations in organelle homeostasis.