CR6 interacting factor 1 deficiency induces premature senescence via SIRT3 inhibition in endothelial cells.

CR6 interacting factor 1 deficiency induces premature senescence via SIRT3 inhibition in endothelial cells. Free Radic Biol Med. 2020 Feb 25;: Authors: Kim S, Piao S, Lee I, Nagar H, Choi SJ, Shin N, Kim DW, Shong M, Jeon BH, Kim CS Abstract Vascular endothelial cell senescence is an important cause of cardiac-related diseases. Mitochondrial reactive oxygen species (mtROS) have been implicated in cellular senescence and multiple cardiovascular disorders. CR6 interacting factor 1 (CRIF1) deficiency has been shown to increase mtROS via the inhibition of mitochondrial oxidative phosphorylation; however, the mechanisms by which mtROS regulates vascular endothelial senescence have not been thoroughly explored. The goal of this study was to investigate the effects of CRIF1 deficiency on endothelial senescence and to elucidate the underlying mechanisms. CRIF1 deficiency was shown to increase the activity of senescence-associated β-galactosidase along with increased expression of phosphorylated p53, p21, and p16 proteins. Cell cycle arrested in the G0/G1 phase were identified in CRIF1-deficient cells using the flow cytometry. Furthermore, CRIF1 deficiency was also shown to increase cellular senescence by reducing the expression of Sirtuin 3 (SIRT3) via ubiquitin-mediated degradation of transcription factors PGC1α and NRF2. Downregulation of CRIF1 also attenuated the function of mitochondrial antioxidant enzymes including manganese superoxi...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research