Ferro-Novick Lab
Vesicle traffic, autophagy,and ER quality control
 
The goal of our research program is to understand how intracellular membranes communicate with each other to maintain cellular homeostasis during cell stress
 
Cross-talk between the secretory and autophagy pathways
 
Macroautophagy is a highly conserved catabolic process that uses membrane trafficking machinery to make autophagosomes, distinct organelles that target cellular components for degradation. Basal levels of macroautophagy continuously replenish the cellular pool of amino acids and other metabolites to maintain cellular homeostasis. However, when cells are stressed, macroautophagy is quickly upregulated. This upregulation leads to a dramatic membrane reorganization in the cell to meet the high demand for membrane that is used to form autophagosomes. Recent studies indicate that the membrane needed to form an autophagosome comes in part from the secretory pathway. When macroautophagy is induced, the secretory pathway is downregulated. This down regulation is a consequence of diverting ER-derived COPII coated vesicles, that normally traffic to the Golgi, to the macroautophagy pathway. Understanding how core trafficking machinery interacts with the autophagy machinery during cell stress to maintain homeostasis is one of the focuses of the lab.
 
ER Structure and quality control

The ER has many functions, including lipid synthesis, glycosylation and protein folding. A significant fraction of the proteins that enter the ER do not fold properly and instead accumulate in the lumen of the ER. ER quality control pathways degrade misfolded proteins and maintain ER homeostasis The objective of our studies is to understand a new and exciting ER quality control pathway, called ER phagy, which degrades the ER during cell stress. Recent studies in the lab have focused on how the ER autophagy machinery recognizes misfolded disease-causing proteins and targets these proteins to the lysosome for degradation in mammalian cells. These studies have uncovered novel machinery for the packaging of ER and misfolded cargos into autophagosomes.