ER-Mitochondria Crosstalk during Cerebral Ischemia: Molecular Chaperones and ER-Mitochondrial Calcium Transfer
Figure 1
(a) Diagram of cerebral ischemia-induced cell death signaling cascade. (b) Chaperone machinery controls ER-mitochondria Ca2+ crosstalk at the MAM. Under normal, resting conditions, SIG1R chaperone forms a complex with GRP78 at the ER. Under stress such as ischemia, SIG1R dissociates from GRP78 and associates with IP3R3 at the MAM, and GRP78 translocates from ER to IMM. ER-mitochondria Ca2+ transfer controls cell survival or death decision. Cyt c: cytochrome c; ER: endoplasmic reticulum; GRP75: glucose-regulated protein 75; GRP78: glucose-regulated protein 78 kDa; IMM: inner mitochondrial membrane; IP3R: inositol trisphosphate receptor; MCU: mitochondrial Ca2+ uniporter; Mito: mitochondria; MPTP: mitochondrial permeability transition pore; OMM: outer mitochondrial membrane; SIG1R: sigma-1 receptor; VDAC: voltage-dependent anion channel.
