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IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer.
Bartok, Adam; Weaver, David; Golenár, Tünde; Nichtova, Zuzana; Katona, Máté; Bánsághi, Száva; Alzayady, Kamil J; Thomas, V Kaye; Ando, Hideaki; Mikoshiba, Katsuhiko; Joseph, Suresh K; Yule, David I; Csordás, György; Hajnóczky, György.
Afiliação
  • Bartok A; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Weaver D; Departent of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
  • Golenár T; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Nichtova Z; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Katona M; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Bánsághi S; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Alzayady KJ; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
  • Thomas VK; Department of Physiology and Pharmacology, University of Rochester, Rochester, NY, USA.
  • Ando H; Department of Physiology and Pharmacology, University of Rochester, Rochester, NY, USA.
  • Mikoshiba K; Lab for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, Japan.
  • Joseph SK; Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
  • Yule DI; Lab for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, Japan.
  • Csordás G; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210, Shanghai, China.
  • Hajnóczky G; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Nat Commun ; 10(1): 3726, 2019 08 19.
Article em En | MEDLINE | ID: mdl-31427578
ABSTRACT
Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP3 receptors (IP3R) and the mitochondrial calcium uniporter, and are central to cell survival. It remains unclear whether IP3Rs also have a structural role in contact formation and whether the different IP3R isoforms have redundant functions. Using an IP3R-deficient cell model rescued with each of the three IP3R isoforms and an array of super-resolution and ultrastructural approaches we demonstrate that IP3Rs are required for maintaining ER-mitochondrial contacts. This role is independent of calcium fluxes. We also show that, while each isoform can support contacts, type 2 IP3R is the most effective in delivering calcium to the mitochondria. Thus, these studies reveal a non-canonical, structural role for the IP3Rs and direct attention towards the type 2 IP3R that was previously neglected in the context of ER-mitochondrial calcium signaling.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canais de Cálcio / Sinalização do Cálcio / Retículo Endoplasmático / Receptores de Inositol 1,4,5-Trifosfato / Mitocôndrias Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Canais de Cálcio / Sinalização do Cálcio / Retículo Endoplasmático / Receptores de Inositol 1,4,5-Trifosfato / Mitocôndrias Limite: Animals / Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos