IP<sub>3</sub> receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31427578.
- Also identified by DOI 10.1038/s41467-019-11646-3 and PMC identifier 6700175.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP<sub>3</sub> 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.
Medical subject headings
- Calcium Channels
- Calcium Signaling
- Endoplasmic Reticulum
- Inositol 1,4,5-Trisphosphate Receptors
- Mitochondria