TRPC3 shapes the ER-mitochondria Ca2+ ...
Document type :
Compte-rendu et recension critique d'ouvrage
PMID :
Title :
TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence
Author(s) :
Farfariello, Valerio [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gordienko, Dmitri [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Mesilmany, Lina [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth] [LU / ULB]
Touil, Yasmine [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Germain, Emmanuelle [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Fliniaux, Ingrid [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Desruelles, Emilie [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gkika, Dimitra [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Roudbaraki, Morad [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Shapovalov, George [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Noyer, Lucile [Auteur]
New York University Langone Medical Center [NYU Langone Medical Center]
Lebas, Mathilde [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Allart, Laurent [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
Zienthal-Gelus, Nathalie [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Iamshanova, Oksana [Auteur]
Universität Bern / University of Bern [UNIBE]
Bonardi, Franck [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Université de Lille
Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
Figeac, Martin [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Université de Lille
Plateforme de génomique fonctionnelle et structurelle [Lille]
Laine, William [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Kluza, Jerome [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Marchetti, Philippe [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Quesnel, Bruno [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Metzger, Daniel [Auteur]
Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC]
Bernard, David [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Centre Léon Bérard [Lyon]
Parys, Jan [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Lemonnier, Loïc [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Prevarskaya, Natalia [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gordienko, Dmitri [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Mesilmany, Lina [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
الجامعة اللبنانية [بيروت] = Lebanese University [Beirut] = Université libanaise [Beyrouth] [LU / ULB]
Touil, Yasmine [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Germain, Emmanuelle [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Fliniaux, Ingrid [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Desruelles, Emilie [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Gkika, Dimitra [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Roudbaraki, Morad [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Shapovalov, George [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Noyer, Lucile [Auteur]
New York University Langone Medical Center [NYU Langone Medical Center]
Lebas, Mathilde [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Allart, Laurent [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
Zienthal-Gelus, Nathalie [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Iamshanova, Oksana [Auteur]
Universität Bern / University of Bern [UNIBE]
Bonardi, Franck [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Université de Lille
Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique]
Figeac, Martin [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Université de Lille
Plateforme de génomique fonctionnelle et structurelle [Lille]
Laine, William [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Kluza, Jerome [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Marchetti, Philippe [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Quesnel, Bruno [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Metzger, Daniel [Auteur]
Institut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC]
Bernard, David [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Centre Léon Bérard [Lyon]
Parys, Jan [Auteur]
Catholic University of Leuven = Katholieke Universiteit Leuven [KU Leuven]
Lemonnier, Loïc [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Prevarskaya, Natalia [Auteur]
Laboratoire de Physiologie Cellulaire - U 1003 [PHYCELL]
Journal title :
Nature Communications
Pages :
956
Publisher :
Nature Publishing Group
Publication date :
2022-02-17
ISSN :
2041-1723
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Abstract Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We ...
Show more >Abstract Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering mitochondrial function and OXPHOS in stress-induced senescent fibroblasts. We demonstrate that TRPC3 protein, acting as a controller of mitochondrial Ca 2+ load via negative regulation of IP 3 receptor-mediated Ca 2+ release, is down regulated in senescence regardless of the type of senescence inducer. This remodelling promotes cytosolic/mitochondrial Ca 2+ oscillations and elevates mitochondrial Ca 2+ load, mitochondrial oxygen consumption rate and oxidative phosphorylation. Re-expression of TRPC3 in senescent cells diminishes mitochondrial Ca 2+ load and promotes escape from OIS-induced senescence. Cellular senescence evoked by TRPC3 downregulation in stromal cells displays a proinflammatory and tumour-promoting secretome that encourages cancer epithelial cell proliferation and tumour growth in vivo. Altogether, our results unravel the mechanism contributing to pro-tumour behaviour of senescent cells.Show less >
Show more >Abstract Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering mitochondrial function and OXPHOS in stress-induced senescent fibroblasts. We demonstrate that TRPC3 protein, acting as a controller of mitochondrial Ca 2+ load via negative regulation of IP 3 receptor-mediated Ca 2+ release, is down regulated in senescence regardless of the type of senescence inducer. This remodelling promotes cytosolic/mitochondrial Ca 2+ oscillations and elevates mitochondrial Ca 2+ load, mitochondrial oxygen consumption rate and oxidative phosphorylation. Re-expression of TRPC3 in senescent cells diminishes mitochondrial Ca 2+ load and promotes escape from OIS-induced senescence. Cellular senescence evoked by TRPC3 downregulation in stromal cells displays a proinflammatory and tumour-promoting secretome that encourages cancer epithelial cell proliferation and tumour growth in vivo. Altogether, our results unravel the mechanism contributing to pro-tumour behaviour of senescent cells.Show less >
Language :
Anglais
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Non
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