As the holiday season approaches, many scientists are preparing to adjust their habits to cope with the occasional stress arising from the conflict between the demands of the lab and family. Stress is also sensed at the cellular level, and there is growing evidence that an imbalance in lipid homeostasis triggers compensatory alterations in metabolism to relieve stress and rebalance the system.
The endoplasmic reticulum is a principal site for membrane biogenesis and a major distribution hub for lipid trafficking to and from the cell. It is not surprising, then, that the endoplasmic reticulum (ER) is the focus of the cellular response to stress arising from lipid overload or lipid depletion. The ER stress response has been defined by delineating the biochemical signals and associated adaptations triggered by misfolded ER lumenal proteins or defects in protein glycosylation. Those stressors, acting through their downstream transcriptional effectors, also elicit significant changes in lipid metabolism, linking ER lipid homeostasis and protein quality control.
The transcriptional changes activated by ER stress target the biosynthetic pathways for cholesterol, fatty acid, phospholipid and/or triglyceride biosynthesis and can result in significant alterations in lipid composition, depending on the cell lineage and nature of the stress. Fatty acids, whether derived from the diet or synthesized de novo, are destined for either destruction by oxidation or incorporation into membrane structural lipids. If the fatty acid supply exceeds the capacity of these two processes, the excess fatty acids are converted to cholesterol esters and triglycerides and packaged into lipid droplets. Lipid droplet accumulation serves as an outlet to relieve the stress of fatty acid overload on ER membrane lipid biogenesis.
In September, the 50th International Conference on the Bioscience of Lipids was held in Regensburg, Germany. The five-day meeting focused on the biological and regulatory functions of lipid molecular species, but each session had presentations that touched on factors that govern lipid homeostasis and lipid droplet formation.
The presentations reflected the early development of LipidomicNet, the European Union Framework VII project focused on the structure of lipid droplets and their function in human health and disease that kicked off just last year. Lipid droplet formation is a hallmark of “energy-overload” metabolic diseases that are a major heath concern. One goal of LipidomicNet is to integrate lipid structure profiles with proteome and transcriptome analysis to reveal the interrelationship between gene expression and lipid droplet formation.
The project also manages the LipidomicNetWiki (www.lipidomicnet.org), in close collaboration with LIPID Metabolites and Pathways Strategy (LIPID MAPS) and Lipid Bank-Japan. One hope is that those investigators who “bump” into lipid metabolism in their work will take advantage of the LipidomicsWiki to help sort out the cellular responses to metabolic stress.
All members of the Lipidomics Expertise Platform are allowed to edit and add content to LipidomicNet-Wiki, so I encourage you to register with the LEP (http://bit.ly/2Y2nOo) and start contributing.
As for preventing holiday stress, I recommend watching out for lipid overload!
Suzanne Jackowski (email@example.com) is a member of the department of infectious diseases at St. Jude Children’s Research Hospital.