Molecular, Cell and Cancer Biology
First Thesis Advisor
Eric Baehrecke, Ph.D.
autophagy, regulatory mechanisms, Drosophila, Mcr
Autophagy is a conserved process that cells use to degrade their own cytoplasmic components by delivery to lysosomes. Autophagy ensures intracellular quality control and is associated with diseases such as cancer and immune disorders. The process of autophagy is controlled by core autophagy (Atg) genes that are conserved from yeast to mammal. Most Atg proteins and their regulators were identified through pioneering studies of the single cell yeast Saccharomyces cerevisiae, and little is known about factors that systematically coordinate autophagy within the tissues of multicellular animals. The goal of this thesis is to identify new autophagy regulators and provide a better understanding of the regulatory mechanisms within multicellular animals. My research determined Macroglobulin complement-related (Mcr), a Drosophila complement orthologue, can activate autophagy during developmental cell death. Unlike most known autophagy regulators, Mcr functions in a cell non-autonomous manner to trigger autophagy in neighboring cells. To my knowledge, this is the first identified autophagy factor that cell non-autonomously activates autophagy. Additionally, I found that Mcr, a secreted protein, instructs the autophagy machinery through the immune receptor Draper, suggesting a relationship between autophagy and the control of inflammation. Lastly, Mcr is dispensable for both nutrient deprivation-induced autophagy in the fat body and developmentally programmed autophagy in the dying midgut of Drosophila. Therefore, this study unveils a mechanism in a multicellular organism by which autophagy is systematically controlled in distinct cell contexts.
Lin, L. Complement-Related Regulates Autophagy in Neighboring Cells. (2017). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 911. DOI: 10.13028/M2G09W. https://escholarship.umassmed.edu/gsbs_diss/911
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