Open Access System for Information Sharing

Login Library

 

Article
Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM

Title
DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM
Authors
KIM, JOUNG HUN
POSTECH Authors
KIM, JOUNG HUN
Date Issued
Dec-2017
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
http://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
Files in This Item:

qr_code

  • mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher

 KIM, JOUNG HUN
Dept of Life Sciences
Read more

Altmetric

Views & Downloads

Browse