Počet záznamů: 1
Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death
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SYSNO ASEP 0481503 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death Tvůrce(i) Blecha, Jan (BTO-N)
Novais, Silvia Magalhaes (BTO-N)
Rohlenová, Kateřina (BTO-N) ORCID, RID
Novotná, Eliška (BTO-N)
Lettlová, Sandra (BTO-N)
Schmitt, S. (DE)
Zischka, H. (DE)
Neužil, Jiří (BTO-N) RID
Rohlena, Jakub (BTO-N) RID, ORCIDCelkový počet autorů 9 Zdroj.dok. Free Radical Biology and Medicine. - : Elsevier - ISSN 0891-5849
Roč. 112, NOV 2017 (2017), s. 253-266Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova Electron transport chain ; Supercomplexes ; Antioxidant defense ; SOD2 Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology CEP GA16-22823S GA ČR - Grantová agentura ČR GA17-20904S GA ČR - Grantová agentura ČR GA16-12719S GA ČR - Grantová agentura ČR NV16-31604A GA MZd - Ministerstvo zdravotnictví LM2015062 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy LQ1604 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora BTO-N - RVO:86652036 UT WOS 000411829300022 EID SCOPUS 85026789016 DOI 10.1016/j.freeradbiomed.2017.07.033 Anotace Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting. Mechanistically, this is mediated by the increased detoxification of ETC-derived ROS by mitochondrial antioxidant defense, principally by the superoxide dismutase 2 thioredoxin axis. In contrast, under conditions of glucose limitation, cell death is induced preferentially in quiescent cells and is correlated with intracellular ATP depletion but not with ROS. This is related to the inability of quiescent cells to compensate for the lost mitochondrial ATP production by the upregulation of glucose uptake. Hence, elevated ROS, not the loss of mitochondrially-generated ATP, are responsible for cell death induction by ETC disruption in ample nutrients condition, e.g. in well perfused healthy tissues, where antioxidant defense imparts specificity. However, in conditions of limited glucose, e.g. in poorly perfused tumors, ETC disruption causes rapid depletion of cellular ATP, optimizing impact towards tumor-associated dormant cells. In summary, we propose that antioxidant defense in quiescent cells is aided by local glucose limitations to ensure selectivity of ETC inhibition-induced cell death. Pracoviště Biotechnologický ústav Kontakt Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Rok sběru 2018
Počet záznamů: 1