Fig. 1
From: Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases
The putative model of Sig-1R at the MAM. a In the normal state, the Sig-1R interacts with BiP. Upon agonist stimulation or the decline of ER Ca2+, the Sig-1R dissociates from BiP to stabilize the IP3R3 for Ca2+ signaling from ER into mitochondria and to regulate the IRE1-dependent pathway to counteract the ER stress. The Sig-1R protects against apoptosis and ROS via the Bcl-2- or Nrf2-dependent pathways. Sig-1Rs can also associate with VDAC2 or Rac1. b The depletion of Sig-1R leads to an abnormal Ca2+ signaling between ER and mitochondria and the disruption of the ATP production. Enhanced ROS production, increased cytochrome c release, or reduced Bcl-2 can cause ER stress that leads to the collapse of the MAM and consequently enhanced autophagy or apoptotic cell death