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Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism

Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualiz...

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Autores principales: Katona, Máté, Bartók, Ádám, Nichtova, Zuzana, Csordás, György, Berezhnaya, Elena, Weaver, David, Ghosh, Arijita, Várnai, Péter, Yule, David I., Hajnóczky, György
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646835/
https://www.ncbi.nlm.nih.gov/pubmed/36351901
http://dx.doi.org/10.1038/s41467-022-34365-8
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author Katona, Máté
Bartók, Ádám
Nichtova, Zuzana
Csordás, György
Berezhnaya, Elena
Weaver, David
Ghosh, Arijita
Várnai, Péter
Yule, David I.
Hajnóczky, György
author_facet Katona, Máté
Bartók, Ádám
Nichtova, Zuzana
Csordás, György
Berezhnaya, Elena
Weaver, David
Ghosh, Arijita
Várnai, Péter
Yule, David I.
Hajnóczky, György
author_sort Katona, Máté
collection PubMed
description Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP(3) receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca(2+) coupling, IP3Rs captured at mitochondria promptly mediate Ca(2+) transfer, stimulating mitochondrial oxidative metabolism. The Ca(2+) transfer does not require linkage with a pore-forming protein in the outer mitochondrial membrane. Thus, motile IP3Rs can traffic in and out of ERMCs, and, when ‘parked’, mediate calcium signal propagation to the mitochondria, creating a dynamic arrangement that supports local communication.
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spelling pubmed-96468352022-11-15 Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism Katona, Máté Bartók, Ádám Nichtova, Zuzana Csordás, György Berezhnaya, Elena Weaver, David Ghosh, Arijita Várnai, Péter Yule, David I. Hajnóczky, György Nat Commun Article Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP(3) receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca(2+) coupling, IP3Rs captured at mitochondria promptly mediate Ca(2+) transfer, stimulating mitochondrial oxidative metabolism. The Ca(2+) transfer does not require linkage with a pore-forming protein in the outer mitochondrial membrane. Thus, motile IP3Rs can traffic in and out of ERMCs, and, when ‘parked’, mediate calcium signal propagation to the mitochondria, creating a dynamic arrangement that supports local communication. Nature Publishing Group UK 2022-11-09 /pmc/articles/PMC9646835/ /pubmed/36351901 http://dx.doi.org/10.1038/s41467-022-34365-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Katona, Máté
Bartók, Ádám
Nichtova, Zuzana
Csordás, György
Berezhnaya, Elena
Weaver, David
Ghosh, Arijita
Várnai, Péter
Yule, David I.
Hajnóczky, György
Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism
title Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism
title_full Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism
title_fullStr Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism
title_full_unstemmed Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism
title_short Capture at the ER-mitochondrial contacts licenses IP(3) receptors to stimulate local Ca(2+) transfer and oxidative metabolism
title_sort capture at the er-mitochondrial contacts licenses ip(3) receptors to stimulate local ca(2+) transfer and oxidative metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9646835/
https://www.ncbi.nlm.nih.gov/pubmed/36351901
http://dx.doi.org/10.1038/s41467-022-34365-8
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