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Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2
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SYSNO ASEP 0520704 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2 Author(s) Hubáčková, Soňa (BTO-N)
Davidová, Eliška (BTO-N)
Rohlenová, Kateřina (BTO-N) ORCID, RID
Štursa, Jan (BTO-N)
Werner, Lukáš (BTO-N)
Anděra, Ladislav (BTO-N)
Dong, L. (AU)
Terp, M. G. (DK)
Hodný, Zdeněk (UMG-J) RID
Ditzel, H. J. (DK)
Rohlena, Jakub (BTO-N) RID, ORCID
Neužil, Jiří (BTO-N) RIDNumber of authors 12 Source Title Cell Death and Differentiation. - : Springer - ISSN 1350-9047
Roč. 26, č. 2 (2019), s. 276-290Number of pages 15 s. Language eng - English Country US - United States Keywords oncogene-induced senescence ; cellular senescence ; oxidative stress ; dna-damage Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology Subject RIV - cooperation Institute of Molecular Genetics - Genetics ; Molecular Biology R&D Projects GA18-02550S GA ČR - Czech Science Foundation (CSF) GA17-07635S GA ČR - Czech Science Foundation (CSF) GA15-02203S GA ČR - Czech Science Foundation (CSF) GA16-22823S GA ČR - Czech Science Foundation (CSF) GA17-20904S GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000455715000006 DOI 10.1038/s41418-018-0118-3 Annotation 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2020 Electronic address https://www.nature.com/articles/s41418-018-0118-3
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