Endoplasmic Reticulum and Mitochondrial Stress Pathways

The **Endoplasmic Reticulum and Mitochondrial Stress Pathways** refer to the integrated and tightly regulated signaling networks that connect the endoplasmic reticulum and mitochondria in response to cellular stressors. These pathways involve the unfolded protein response of the ER (UPR^ER^), the mitochondrial unfolded protein response (UPR^mt^), and direct organelle contact sites (such as mitochondria-associated membranes, MAMs), allowing for coordinated regulation of proteostasis, calcium homeostasis, metabolism, and cell death. Disruption or dysregulation of these interactions contributes to diverse disease mechanisms, linking organelle stress to inflammation, apoptosis, and metabolic dysfunction[1][2][3][5][6][7]. The molecular biology of these pathways encompasses many proteins, including ER-membrane sensors (PERK, IRE1, ATF6), mitochondrial chaperones, ion channels (IP3R, VDAC), and tethering proteins (e.g., Mitofusin 2), among others[1][2].\n\nThis is not a single target or receptor, but a functional and structural interface between organelle stress responses.

Other names

ER–mitochondrial stress signalingER–mitochondria axisER stress response and mitochondrial stress responseER-mitochondrial communication pathways

Not applicable to this pathway as a whole; involved drug mechanisms may include UPR modulation, ISR modulation, chaperone activity enhancement, or Ca²⁺ transport modulation.