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

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

SUBMITTER: Farfariello V 

PROVIDER: S-EPMC8854551 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature