EPRS
EPRs: Unraveling the Enigma of Endoplasmic Reticulum Stress
Description
Endoplasmic reticulum stress (ER stress) is a cellular response triggered by the accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), a crucial organelle responsible for protein folding and secretion. When ER stress persists, it can lead to the activation of specific signaling pathways known as unfolded protein responses (UPRs), which aim to restore ER homeostasis or initiate cell death if the stress is irreparable.
The three main branches of UPRs include:
- PERK (PKR-like ER kinase): Phosphorylates eIF2α, which inhibits protein synthesis and promotes the translation of specific mRNAs, including those encoding ER chaperones.
- IRE1 (Inositol-requiring enzyme 1): Splices XBP1 mRNA to produce a spliced form that activates transcription of ER-resident chaperones and ER-associated degradation (ERAD) components.
- ATF6 (Activating transcription factor 6): Translocated to the Golgi apparatus and activates the transcription of ER chaperones and other proteins involved in ER folding and ERAD.
Under normal conditions, UPRs play a protective role in maintaining ER function. However, prolonged or severe ER stress can overwhelm the UPRs, leading to the activation of pro-apoptotic pathways and cell death.
Associated Diseases
ER stress has been implicated in the pathogenesis of numerous diseases, including:
- Neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease)
- Metabolic disorders (e.g., diabetes, obesity)
- Cardiovascular diseases (e.g., atherosclerosis)
- Inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease)
- Cancer
Did you Know ?
Studies have shown that approximately 30% of all proteins synthesized in mammalian cells are processed through the ER, highlighting the critical role of ER stress in cellular function.
