| First Author | Park SJ | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 10 | Pages | 2748-2759 |
| PubMed ID | 29212023 | Mgi Jnum | J:254274 |
| Mgi Id | MGI:6104173 | Doi | 10.1016/j.celrep.2017.11.043 |
| Citation | Park SJ, et al. (2017) DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca(2+) Transfer through the MAM. Cell Rep 21(10):2748-2759 |
| abstractText | A wide range of Ca(2+)-mediated functions are enabled by the dynamic properties of Ca(2+), all of which are dependent on the endoplasmic reticulum (ER) and mitochondria. Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that is involved in the function of intracellular organelles and is linked to cognitive and emotional deficits. Here, we demonstrate that DISC1 localizes to the mitochondria-associated ER membrane (MAM). At the MAM, DISC1 interacts with IP3R1 and downregulates its ligand binding, modulating ER-mitochondria Ca(2+) transfer through the MAM. The disrupted regulation of Ca(2+) transfer caused by DISC1 dysfunction leads to abnormal Ca(2+) accumulation in mitochondria following oxidative stress, which impairs mitochondrial functions. DISC1 dysfunction alters corticosterone-induced mitochondrial Ca(2+) accumulation in an oxidative stress-dependent manner. Together, these findings link stress-associated neural stimuli with intracellular ER-mitochondria Ca(2+) crosstalk via DISC1, providing mechanistic insight into how environmental risk factors can be interpreted by intracellular pathways under the control of genetic components in neurons. |
