DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM
SCIE
SCOPUS
- Title
- DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM
- Authors
- Park, Sung Jin; Lee, Su Been; Suh, Yeongjun; Kim, Su-Jeong; Lee, Namgyu; Hong, Ji-Ho; Park, Cana; Woo, Youngsik; Ishizuka, Koko; KIM, JOUNG HUN; Berggren, Per-Olof; Sawa, Akira; PARK, SANG KI
- Date Issued
- 2017-12
- Publisher
- Cell Press
- Abstract
- A wide range of Ca2+-mediated functions are enabled by the dynamic properties of Ca2+, 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 Ca2+ transfer through the MAM. The disrupted regulation of Ca2+ transfer caused by DISC1 dysfunction leads to abnormal Ca2+ accumulation in mitochondria following oxidative stress, which impairs mitochondrial functions. DISC1 dysfunction alters corticosterone-induced mitochondrial Ca2+ accumulation in an oxidative stress-dependent manner. Together, these findings link stress-associated neural stimuli with intracellular ER-mitochondria Ca2+ 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.
- Keywords
- DISC1, MAM, mitochondria, Ca2+, IP3R1, oxidative stress
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/38947
- DOI
- 10.1016/j.celrep.2017.11.043
- ISSN
- 2211-1247
- Article Type
- Article
- Citation
- Cell Reports, vol. 21, no. 10, page. 2748 - 2759, 2017-12
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