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Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2

S. Hubackova, E. Davidova, K. Rohlenova, J. Stursa, L. Werner, L. Andera, L. Dong, MG. Terp, Z. Hodny, HJ. Ditzel, J. Rohlena, J. Neuzil,

. 2019 ; 26 (2) : 276-290. [pub] 20180521

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20022927
E-zdroje Online Plný text

NLK Free Medical Journals od 2011
PubMed Central od 2011 do Před 1 rokem
Europe PubMed Central od 2011 do Před 1 rokem
ProQuest Central od 2000-01-01 do Před 1 rokem
Open Access Digital Library od 1997-01-01
Health & Medicine (ProQuest) od 2000-01-01 do Před 1 rokem

Odkazy

PubMed 29786070
DOI 10.1038/s41418-018-0118-3
Knihovny.cz E-zdroje

Cellular senescence is a form of cell cycle arrest that limits the proliferative potential of cells, including tumour cells. However, inability of immune cells to subsequently eliminate senescent cells from the organism may lead to tissue damage, inflammation, enhanced carcinogenesis and development of age-related diseases. We found that the anticancer agent mitochondria-targeted tamoxifen (MitoTam), unlike conventional anticancer agents, kills cancer cells without inducing senescence in vitro and in vivo. Surprisingly, it also selectively eliminates both malignant and non-cancerous senescent cells. In naturally aged mice treated with MitoTam for 4 weeks, we observed a significant decrease of senescence markers in all tested organs compared to non-treated animals. Mechanistically, we found that the susceptibility of senescent cells to MitoTam is linked to a very low expression level of adenine nucleotide translocase-2 (ANT2), inherent to the senescent phenotype. Restoration of ANT2 in senescent cells resulted in resistance to MitoTam, while its downregulation in non-senescent cells promoted their MitoTam-triggered elimination. Our study documents a novel, translationally intriguing role for an anticancer agent targeting mitochondria, that may result in a new strategy for the treatment of age-related diseases and senescence-associated pathologies.

Citace poskytuje Crossref.org

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