Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00520704" target="_blank" >RIV/68378050:_____/19:00520704 - isvavai.cz</a>
Alternative codes found
RIV/86652036:_____/19:00520704 RIV/00216208:11310/19:10405278
Result on the web
<a href="https://www.nature.com/articles/s41418-018-0118-3" target="_blank" >https://www.nature.com/articles/s41418-018-0118-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41418-018-0118-3" target="_blank" >10.1038/s41418-018-0118-3</a>
Alternative languages
Result language
angličtina
Original language name
Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Death and Differentiation
ISSN
1350-9047
e-ISSN
—
Volume of the periodical
26
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
276-290
UT code for WoS article
000455715000006
EID of the result in the Scopus database
—