AI Article Synopsis
- Lipid composition varies greatly between different organelles and membrane leaflets, and maintaining lipid balance is essential to prevent diseases
- Researchers developed a model system to study the effects of lipid imbalance using quantitative lipid profiling, which helped reveal significant changes in cell biochemistry
- The study introduced the "membrane stress response" (MSR), showing that instead of restoring lipid balance, cells adapt by remodeling their protein management systems, particularly through the unfolded protein response (UPR), which protects against dysfunction in lipid-disrupted cells
Article Abstract
Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the "membrane stress response" (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity-functions otherwise lethally compromised in lipid dysregulated cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496426 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2012.08.016 | DOI Listing |
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