Tag: Cellular stress responses

ATF6 is an ER stress‑responsive transcription factor that enhances protein‑folding capacity and strengthens ER‑associated degradation. After trafficking to the Golgi and undergoing regulated proteolysis, ATF6 activates genes that restore ER proteostasis during unfolded protein accumulation.

Apoptosis is a controlled form of programmed cell death that removes damaged or unnecessary cells without causing inflammation. Through coordinated activation of extrinsic and intrinsic pathways, apoptosis maintains tissue homeostasis and protects organisms from disease.

ER stress arises when misfolded proteins accumulate in the endoplasmic reticulum, overwhelming its folding capacity. Through IRE1, PERK and ATF6 signalling, the unfolded protein response restores proteostasis, reduces protein load and protects cells from stress‑induced damage.

Ferroptosis is a regulated form of cell death characterised by iron‑dependent lipid peroxidation and catastrophic membrane damage. Unlike apoptosis, necroptosis…

Programmed cell death (PCD) is a regulated biological process that eliminates damaged or unnecessary cells through apoptosis, autophagic cell death and regulated necrosis. By maintaining tissue homeostasis and supporting stress adaptation, PCD is essential for development and long‑term organismal health.

Necroptosis is a regulated necrotic cell‑death pathway driven by RIPK1–RIPK3–MLKL signalling. Through membrane permeabilisation and inflammatory activation, necroptosis eliminates infected or damaged cells when apoptosis is blocked, shaping immunity and disease progression.

RIPK1 is a central signalling kinase that determines whether a cell survives, undergoes apoptosis or triggers necroptosis. Through context‑dependent interactions with TNFR1, caspase‑8, RIPK3 and MLKL, RIPK1 integrates inflammatory cues and stress signals to regulate cell fate.

RIPK3 is a central necroptotic kinase that phosphorylates MLKL and drives regulated necrotic cell death. Through necrosome formation with RIPK1 and activation of inflammatory signalling, RIPK3 shapes immunity, tissue injury and disease progression.

MLKL is the terminal effector of necroptosis. After phosphorylation by RIPK3, MLKL oligomerises and inserts into the plasma membrane, causing membrane rupture and release of inflammatory DAMPs. MLKL is essential for regulated necrotic cell death and immune activation.

ERAD is a central ER quality‑control pathway that recognises misfolded proteins, retrotranslocates them to the cytosol, ubiquitinates them and directs them to the proteasome. By preventing proteotoxic accumulation, ERAD preserves ER homeostasis and supports cellular proteostasis.

PERK is a central ER stress sensor that phosphorylates eIF2α, reduces protein synthesis and activates ATF4‑dependent transcription. Through adaptive and apoptotic signalling, PERK coordinates unfolded protein response pathways that restore proteostasis or eliminate irreparably damaged cells.

IRE1 is the most conserved ER stress sensor, activating XBP1 splicing and RIDD to restore proteostasis. Through its kinase and RNase activities, IRE1 detects misfolded proteins, initiates adaptive signalling and coordinates the unfolded protein response during ER stress.

The proteostasis network is an integrated system of chaperones, degradation pathways and organelle‑specific quality‑control mechanisms that maintains protein folding, stability and function. By coordinating refolding, repair and degradation, cells prevent proteotoxic stress and preserve homeostasis.

The unfolded protein response (UPR) is a conserved ER stress pathway that detects misfolded proteins and restores proteostasis. Through IRE1, PERK and ATF6 signalling, cells expand folding capacity, reduce protein load and maintain homeostasis under conditions of ER stress.

The heat‑shock response (HSR) is a conserved cellular defence pathway that protects the proteome under stress. By activating HSF1 and inducing heat‑shock proteins, cells stabilise protein folding, prevent aggregation and restore proteostasis during proteotoxic conditions.