Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence

Clotilde Wiel, Hélène Lallet-Daher, Delphine Gitenay, Baptiste Gras, Benjamin Le Calvé, Arnaud Augert, Mylène Ferrand, Natalia Prevarskaya, Hélène Simonnet, David Vindrieux, David Bernard

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

Senescence is involved in various pathophysiological conditions. Besides loss of retinoblastoma and p53 pathways, little is known about other pathways involved in senescence. Here we identify two calcium channels; inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (also known as inositol 1,4,5-triphosphate receptor 2 (IP3R2)) and mitochondrial calcium uniporter (MCU) as new senescence regulators in a loss-of-function genetic screen. We show that loss of ITPR2, known to mediate endoplasmic reticulum (ER) calcium release, as well as loss of MCU, necessary for mitochondrial calcium uptake, enable escape from oncogene-induced senescence (OIS). During OIS, ITPR2 triggers calcium release from the ER, followed by mitochondrial calcium accumulation through MCU channels. Mitochondrial calcium accumulation leads to a subsequent decrease in mitochondrial membrane potential, reactive oxygen species accumulation and senescence. This ER-mitochondria calcium transport is not restricted to OIS, but is also involved in replicative senescence. Our results show a functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria.

langue originaleAnglais
Pages (de - à)3792
journalNature Communications
Volume5
Les DOIs
étatPublié - 2014
Modification externeOui

Empreinte digitale

inositols
Inositol 1,4,5-Trisphosphate Receptors
endoplasmic reticulum
Endoplasmic Reticulum
calcium
Calcium
Oncogenes
oncogenes
Mitochondria
Calcium Channels
mitochondria
Retinoblastoma
Mitochondrial Membrane Potential
Cell Aging
Reactive Oxygen Species
regulators
Membranes
escape

Citer ceci

Wiel, Clotilde ; Lallet-Daher, Hélène ; Gitenay, Delphine ; Gras, Baptiste ; Le Calvé, Benjamin ; Augert, Arnaud ; Ferrand, Mylène ; Prevarskaya, Natalia ; Simonnet, Hélène ; Vindrieux, David ; Bernard, David. / Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence. Dans: Nature Communications. 2014 ; Vol 5. p. 3792.
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title = "Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence",
abstract = "Senescence is involved in various pathophysiological conditions. Besides loss of retinoblastoma and p53 pathways, little is known about other pathways involved in senescence. Here we identify two calcium channels; inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (also known as inositol 1,4,5-triphosphate receptor 2 (IP3R2)) and mitochondrial calcium uniporter (MCU) as new senescence regulators in a loss-of-function genetic screen. We show that loss of ITPR2, known to mediate endoplasmic reticulum (ER) calcium release, as well as loss of MCU, necessary for mitochondrial calcium uptake, enable escape from oncogene-induced senescence (OIS). During OIS, ITPR2 triggers calcium release from the ER, followed by mitochondrial calcium accumulation through MCU channels. Mitochondrial calcium accumulation leads to a subsequent decrease in mitochondrial membrane potential, reactive oxygen species accumulation and senescence. This ER-mitochondria calcium transport is not restricted to OIS, but is also involved in replicative senescence. Our results show a functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria.",
keywords = "Calcium, Cell Aging, Endoplasmic Reticulum, Humans, Inositol 1,4,5-Trisphosphate Receptors, Membrane Potential, Mitochondrial, Mitochondria, Oncogenes, Oxidative Stress, Journal Article, Research Support, Non-U.S. Gov't",
author = "Clotilde Wiel and H{\'e}l{\`e}ne Lallet-Daher and Delphine Gitenay and Baptiste Gras and {Le Calv{\'e}}, Benjamin and Arnaud Augert and Myl{\`e}ne Ferrand and Natalia Prevarskaya and H{\'e}l{\`e}ne Simonnet and David Vindrieux and David Bernard",
year = "2014",
doi = "10.1038/ncomms4792",
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journal = "Nature Communications",
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Wiel, C, Lallet-Daher, H, Gitenay, D, Gras, B, Le Calvé, B, Augert, A, Ferrand, M, Prevarskaya, N, Simonnet, H, Vindrieux, D & Bernard, D 2014, 'Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence', Nature Communications, VOL. 5, p. 3792. https://doi.org/10.1038/ncomms4792

Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence. / Wiel, Clotilde; Lallet-Daher, Hélène; Gitenay, Delphine; Gras, Baptiste; Le Calvé, Benjamin; Augert, Arnaud; Ferrand, Mylène; Prevarskaya, Natalia; Simonnet, Hélène; Vindrieux, David; Bernard, David.

Dans: Nature Communications, Vol 5, 2014, p. 3792.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence

AU - Wiel, Clotilde

AU - Lallet-Daher, Hélène

AU - Gitenay, Delphine

AU - Gras, Baptiste

AU - Le Calvé, Benjamin

AU - Augert, Arnaud

AU - Ferrand, Mylène

AU - Prevarskaya, Natalia

AU - Simonnet, Hélène

AU - Vindrieux, David

AU - Bernard, David

PY - 2014

Y1 - 2014

N2 - Senescence is involved in various pathophysiological conditions. Besides loss of retinoblastoma and p53 pathways, little is known about other pathways involved in senescence. Here we identify two calcium channels; inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (also known as inositol 1,4,5-triphosphate receptor 2 (IP3R2)) and mitochondrial calcium uniporter (MCU) as new senescence regulators in a loss-of-function genetic screen. We show that loss of ITPR2, known to mediate endoplasmic reticulum (ER) calcium release, as well as loss of MCU, necessary for mitochondrial calcium uptake, enable escape from oncogene-induced senescence (OIS). During OIS, ITPR2 triggers calcium release from the ER, followed by mitochondrial calcium accumulation through MCU channels. Mitochondrial calcium accumulation leads to a subsequent decrease in mitochondrial membrane potential, reactive oxygen species accumulation and senescence. This ER-mitochondria calcium transport is not restricted to OIS, but is also involved in replicative senescence. Our results show a functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria.

AB - Senescence is involved in various pathophysiological conditions. Besides loss of retinoblastoma and p53 pathways, little is known about other pathways involved in senescence. Here we identify two calcium channels; inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (also known as inositol 1,4,5-triphosphate receptor 2 (IP3R2)) and mitochondrial calcium uniporter (MCU) as new senescence regulators in a loss-of-function genetic screen. We show that loss of ITPR2, known to mediate endoplasmic reticulum (ER) calcium release, as well as loss of MCU, necessary for mitochondrial calcium uptake, enable escape from oncogene-induced senescence (OIS). During OIS, ITPR2 triggers calcium release from the ER, followed by mitochondrial calcium accumulation through MCU channels. Mitochondrial calcium accumulation leads to a subsequent decrease in mitochondrial membrane potential, reactive oxygen species accumulation and senescence. This ER-mitochondria calcium transport is not restricted to OIS, but is also involved in replicative senescence. Our results show a functional role of calcium release by the ITPR2 channel and its subsequent accumulation in the mitochondria.

KW - Calcium

KW - Cell Aging

KW - Endoplasmic Reticulum

KW - Humans

KW - Inositol 1,4,5-Trisphosphate Receptors

KW - Membrane Potential, Mitochondrial

KW - Mitochondria

KW - Oncogenes

KW - Oxidative Stress

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ncomms4792

DO - 10.1038/ncomms4792

M3 - Article

C2 - 24797322

VL - 5

SP - 3792

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -