How do cells spatially organize their metabolism?
To survive in a constantly changing environment, cells must sense nutrient levels and orchestrate metabolic remodeling to respond to changes in nutrient availability. How cells coordinate an organized metabolic response to stresses such as starvation remain poorly understood.
Our lab is interested in how cells spatially organize their metabolism in response to a constantly changing environment. Cellular metabolism can be organized in many different ways. One of the most basic is the compartmentalization of metabolism into membrane-bound organelles. Cells an also utilize non-membrane bound, or phase separated organelles such as stress bodies or cytoplasmic protein aggregates to compartmentalize specific cellular pathways under times of stress.
Our lab is interested in a third way that cells spatially organize their metabolism: at the physical junctions between organelles. These so-called inter-organelle contact sites, or membrane contact sites, serve many roles in adaptive cellular metabolism.
To understand the mechanisms governing inter-organelle contact sites and their roles in metabolism, we utilize yeast as a model system. Recently, we found that yeast ER-vacuole contact sites, called nuclear ER-vacuole junctions (NVJs), serve as unique platforms for coordinating several metabolic pathways. One pathway in particular is the formation of lipid droplets, which accumulate at NVJs in yeast undergoing nutrient stresses such as sugar depletion (Hariri, et al., EMBO Reports, 2017). Indeed, we find that NVJs can serve as a site of lipid droplet biogenesis during times of nutritional stress. NVJ tether Mdm1 appears to coordinate this stress-induced lipid droplet accumulation at the NVJ, and we are currently investigating the mechanisms underlying this.
The lab uses mammalian cell biology, biochemistry, structural biology, and yeast genetics to elucidate novel molecular mechanisms of membrane reshaping and to relate these findings to human pathophysiology and disease