The article reviews the role of redox regulation in the Unfolded Protein Response (UPR) and the formation of Mitochondrial-Endoplasmic Reticulum Contact Sites (MERCS). MERCS are dynamic structures that facilitate communication between mitochondria and the endoplasmic reticulum (ER), mediating material and information exchange, calcium homeostasis, lipid transfer, and mitochondrial dynamics. The UPR, activated by ER stress, involves three branches: IRE1α, PERK, and ATF6, which regulate protein folding, translation, and chaperone expression. Adaptive UPR signaling via MERCS can enhance mitochondrial function, while maladaptive signaling can lead to excessive calcium import and apoptosis. The redox environment in the ER and mitochondria is crucial for maintaining homeostasis, with ROS generation and redox modifications affecting protein function and organelle dynamics. The article highlights the importance of MERCS in regulating Ca2+ flux, mitochondrial dynamics, and the UPR, and discusses the therapeutic potential of targeting UPR signaling and MERCS assembly in age-related conditions such as neurodegeneration and sarcopenia.The article reviews the role of redox regulation in the Unfolded Protein Response (UPR) and the formation of Mitochondrial-Endoplasmic Reticulum Contact Sites (MERCS). MERCS are dynamic structures that facilitate communication between mitochondria and the endoplasmic reticulum (ER), mediating material and information exchange, calcium homeostasis, lipid transfer, and mitochondrial dynamics. The UPR, activated by ER stress, involves three branches: IRE1α, PERK, and ATF6, which regulate protein folding, translation, and chaperone expression. Adaptive UPR signaling via MERCS can enhance mitochondrial function, while maladaptive signaling can lead to excessive calcium import and apoptosis. The redox environment in the ER and mitochondria is crucial for maintaining homeostasis, with ROS generation and redox modifications affecting protein function and organelle dynamics. The article highlights the importance of MERCS in regulating Ca2+ flux, mitochondrial dynamics, and the UPR, and discusses the therapeutic potential of targeting UPR signaling and MERCS assembly in age-related conditions such as neurodegeneration and sarcopenia.