Title: IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer.
Authors: 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
Published In Nat Commun, (2019 08 19)
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.
PubMed ID: 31427578
MeSH Terms: Animals; Calcium Channels/metabolism*; Calcium Signaling/physiology*; Cell Line, Tumor; Cell Survival/physiology; Chickens; Endoplasmic Reticulum/metabolism*; HeLa Cells; Humans; Inositol 1,4,5-Trisphosphate Receptors/genetics; Inositol 1,4,5-Trisphosphate Receptors/metabolism*; Mitochondria/metabolism*; Protein Isoforms/genetics