Adelita Mendoza

Lysosomal remodeling in the zinc homeostatic response

Our research focuses on understanding how cells sense and maintain zinc homeostasis. We focus on how this is achieved at the transcriptional and organelle levels. Lysosomes undergo extensive remodeling in response to fluctuating cytosolic zinc levels. In C. elegans, the zinc importer CDF-2 and zinc exporter ZIPT-2.3 are reciprocally regulated by zinc- in excess zinc CDF-2 levels increase, while ZIPT-2.3 levels decrease. In zinc deficiency, CDF-2 levels decrease, and ZIPT-2.3 levels increase. Super-resolution imaging lysosomes in C. elegans revealed that CDF-2 and ZIPT-2.3 co-localized to lysosomes. Additionally, we observed that lysosomes undergo extensive morphological restructuring in response to fluctuating zinc levels. This remodeling revealed that lysosomes contain an acidified compartment and an expansion compartment. Each compartment contains a specific distribution of zinc transporters. The acidified compartment is acidic and contains zinc, ZIPT-2.3, and CDF-2. The expansion compartment contains CDF-2 alone.

In the Mendoza lab we seek to:

1. Define the significance of the expansion compartment. What is the breadth of its involvement in cellular processes?
2. Understand how lysosomes are created to respond to changes in zinc homeostasis. How is it capable of rapidly responding to ever changing cytosolic zinc levels?
3. Define the structural architecture of lysosomes. Why are lysosomes assembled the way they are?

We adopt a multidisciplinary approach using C. elegans and human cell culture as our model systems. Our toolbox is based in knowledge from cell biology, biochemistry, x-ray physics, analytical chemistry, and molecular biology to answer our questions about how zinc interacts with lysosomes. 

Link to my papers on pubmed

https://pubmed.ncbi.nlm.nih.gov/?term=Adelita+D.++Mendoza