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.

Details

Title
IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer
Author
Bartok, Adam 1 ; Weaver, David 2 ; Golenár, Tünde 2 ; Nichtova, Zuzana 2 ; Katona, Máté 2 ; Bánsághi, Száva 2 ; Alzayady, Kamil J 3 ; V Kaye Thomas 3 ; Ando, Hideaki 4 ; Mikoshiba, Katsuhiko 5 ; Joseph, Suresh K 2 ; Yule, David I 3 ; Csordás, György 2 ; Hajnóczky, György 2   VIAFID ORCID Logo 

1  MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA; Departent of Medical Biochemistry, Semmelweis University, Budapest, Hungary 
2  MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA 
3  Department of Physiology and Pharmacology, University of Rochester, Rochester, NY, USA 
4  Lab for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, Japan; 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, Japan 
5  Lab for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, Japan; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China 
Pages
1-14
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11646-3
ProQuest document ID
2275917452
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.