Organelles in metabolism and stress responses

Ferguson, Shawn M.; Henne, W. Mike

Several presentations also discussed how the endoplasmic reticulum (ER) responds to stress through morphological changes as well as the activation of stress response pathways. Hanaa Hariri (Henne lab, UT Southwestern) showed that the yeast Nuclear ER-Vacuole/lysosome junction (called the NVJ) responds to nutritional stress by becoming a site for lipid droplet (LD) biogenesis. NVJ tether Mdm1 coordinates this LD biogenesis by interacting with fatty acyl-CoA synthases. Her work suggests that yeast strategically position LDs near the vacuole/lysosome during the onset of starvation. Guillaume Thibault (Nanyang Technological University) presented data describing the important role of the ER in lipid homeostasis. Specifically, his group showed that a fully functional unfolded protein response (UPR) is required for regulating proper lipid storage during chronic ER stresses including lipotoxicity. Elaine Mihelc (Purdue University) demonstrated that, in response to the stress of coronavirus infection, the ER morphologically remodels to provide a platform for viral replication and assembly. This leads to viral vesicles that can be ultimately trafficked to lysosomes for degradation. Finally, Brooke Gardner (Martin lab, University of California, Berkeley) presented data showing that the AAA-ATPase Pex1/Pex6 complex functions as a bona fide unfoldase complex that promotes peroxisome biogenesis. This mechanism is similar to that of Cdc48, which functions in ER-associated degradation, and suggests that Pex1/Pex6 can extract other Pex proteins directly from peroxisomal membranes.