Figure 2

Palmitate disturbs intracellular Ca²⁺ homeostasis. ROS activate IP₃R and RYR, which release Ca²⁺ from the ER. The deprivation of ER Ca²⁺ leads to ER stress and CHOP upregulation. Ca²⁺ is transported into mitochondria through a specialized structure composed of IP₃R, VDAC, MCU and GRP75. Excessive Ca²⁺ in mitochondria leads to cytochrome c release. SOC entry triggered by ER Ca²⁺ depletion elicits the persistent influx of Ca²⁺ into cytosol and mitochondria. High intracellular calcium activates calpain signaling. Cytochrome c, CHOP and calpain all provoke caspase activation and cell death. CHOP, CCAAT-enhancer-binding protein homologous protein; GRP75, 75 kDa glucose-regulated protein; MCU, mitochondrial Ca²⁺ uniporter; ROS, reactive oxygen species; SOC, store-operated Ca²⁺; VDAC, voltage-dependent anion channel.