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DISC1 Modulates Neuronal Stress Responses by Gate-Keeping ER-Mitochondria Ca2+ Transfer through the MAM.
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.
Afiliación
  • Park SJ; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Lee SB; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Suh Y; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Kim SJ; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Lee N; Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
  • Hong JH; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Park C; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Woo Y; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Ishizuka K; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kim JH; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea.
  • Berggren PO; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea; The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Sawa A; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Park SK; Department of Life Sciences, Pohang University of Science and Technology, 790-784 Pohang, Republic of Korea. Electronic address: skpark@postech.ac.kr.
Cell Rep ; 21(10): 2748-2759, 2017 Dec 05.
Article en En | MEDLINE | ID: mdl-29212023
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcio / Retículo Endoplásmico / Membranas Intracelulares / Proteínas del Tejido Nervioso / Neuronas Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcio / Retículo Endoplásmico / Membranas Intracelulares / Proteínas del Tejido Nervioso / Neuronas Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos