Show simple item record

dc.contributor.authorPark, Sung Jin
dc.contributor.authorLee, Su Been
dc.contributor.authorSuh, Yeongjun
dc.contributor.authorKim, Su-Jeong
dc.contributor.authorLee, Namgyu
dc.contributor.authorHong, Ji-Ho
dc.contributor.authorPark, Cana
dc.contributor.authorWoo, Youngsik
dc.contributor.authorIshizuka, Koko
dc.contributor.authorKim, Joung-Hun
dc.contributor.authorBerggren, Per-Olof
dc.contributor.authorSawa, Akira
dc.contributor.authorPark, Sang Ki
dc.date2022-08-11T08:09:49.000
dc.date.accessioned2022-08-23T16:44:33Z
dc.date.available2022-08-23T16:44:33Z
dc.date.issued2017-12-05
dc.date.submitted2018-03-29
dc.identifier.citation<p>Cell Rep. 2017 Dec 5;21(10):2748-2759. doi: 10.1016/j.celrep.2017.11.043. <a href="https://doi.org/10.1016/j.celrep.2017.11.043">Link to article on publisher's site</a></p>
dc.identifier.issn2211-1247 (Electronic)
dc.identifier.doi10.1016/j.celrep.2017.11.043
dc.identifier.pmid29212023
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40523
dc.description.abstractA 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29212023&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCa(2+)
dc.subjectDISC1
dc.subjectIP(3)R1
dc.subjectMAM
dc.subjectmitochondria
dc.subjectoxidative stress
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular and Cellular Neuroscience
dc.titleDISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca(2+) Transfer through the MAM
dc.typeJournal Article
dc.source.journaltitleCell reports
dc.source.volume21
dc.source.issue10
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4340&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3329
dc.identifier.contextkey11871287
refterms.dateFOA2022-08-23T16:44:33Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/3329
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.source.pages2748-2759


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
PIIS2211124717316807.pdf
Size:
4.272Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).