TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence

Valerio Farfariello (), Dmitri V. Gordienko, Lina Mesilmany, Yasmine Touil, Emmanuelle Germain, Ingrid Fliniaux, Emilie Desruelles, Dimitra Gkika, Morad Roudbaraki, George Shapovalov, Lucile Noyer, Mathilde Lebas, Laurent Allart, Nathalie Zienthal-Gelus, Oksana Iamshanova, Franck Bonardi, Martin Figeac, William Laine, Jerome Kluza, Philippe Marchetti, Bruno Quesnel, Daniel Metzger, David Bernard, Jan B. Parys, Loïc Lemonnier and Natalia Prevarskaya ()
Additional contact information
Valerio Farfariello: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Dmitri V. Gordienko: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Lina Mesilmany: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Yasmine Touil: UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies
Emmanuelle Germain: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Ingrid Fliniaux: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Emilie Desruelles: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Dimitra Gkika: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Morad Roudbaraki: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
George Shapovalov: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Lucile Noyer: NYU Langone Medical Center
Mathilde Lebas: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Laurent Allart: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Nathalie Zienthal-Gelus: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Oksana Iamshanova: University of Bern
Franck Bonardi: Centre de Biologie et Pathologie
Martin Figeac: Centre de Biologie et Pathologie
William Laine: UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies
Jerome Kluza: UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies
Philippe Marchetti: UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies
Bruno Quesnel: UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies
Daniel Metzger: Université de Strasbourg
David Bernard: Université de Lyon
Jan B. Parys: Department of Cellular and Molecular Medicine & Leuven Kanker Instituut
Loïc Lemonnier: Inserm, U1003 - PHYCEL - Physiologie Cellulaire
Natalia Prevarskaya: Inserm, U1003 - PHYCEL - Physiologie Cellulaire

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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 Ca2+ load via negative regulation of IP3 receptor-mediated Ca2+ release, is down regulated in senescence regardless of the type of senescence inducer. This remodelling promotes cytosolic/mitochondrial Ca2+ oscillations and elevates mitochondrial Ca2+ load, mitochondrial oxygen consumption rate and oxidative phosphorylation. Re-expression of TRPC3 in senescent cells diminishes mitochondrial Ca2+ 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28597-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28597-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28597-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().