Farfariello, Valerio; Gordienko, Dmitri V; Mesilmany, Lina; Touil, Yasmine; Germain, Emmanuelle; Fliniaux, Ingrid; Desruelles, Emilie; Gkika, Dimitra; Roudbaraki, Morad; Shapovalov, George; Noyer, Lucile; Lebas, Mathilde; Allart, Laurent; Zienthal-Gelus, Nathalie; Iamshanova, Oksana; Bonardi, Franck; Figeac, Martin; Laine, William; Kluza, Jerome; Marchetti, Philippe; ... (2022). TRPC3 shapes the ER-mitochondria Ca2+ transfer characterizing tumour-promoting senescence. Nature Communications, 13(1), p. 956. Springer Nature 10.1038/s41467-022-28597-x
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
UniBE Contributor: |
Iamshanova, Oksana |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
21 Feb 2022 08:52 |
Last Modified: |
05 Dec 2022 16:09 |
Publisher DOI: |
10.1038/s41467-022-28597-x |
PubMed ID: |
35177596 |
BORIS DOI: |
10.48350/165769 |
URI: |
https://boris.unibe.ch/id/eprint/165769 |
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