Cell sensitivity to oxidative stress is influenced by ferritin autophagy
2011 (English)In: FREE RADICAL BIOLOGY AND MEDICINE, ISSN 0891-5849, Vol. 50, no 11, 1647-1658 p.Article in journal (Refereed) Published
To test the consequences of lysosomal degradation of differently iron-loaded ferritin molecules and to mimic ferritin autophagy under iron-overload and normal conditions, J774 cells were allowed to endocytose heavily iron loaded ferritin, probably with some adventitious iron (Fe-Ft), or iron-free apo-ferritin (apo-Ft). When cells subsequently were exposed to a bolus dose of hydrogen peroxide, apo-Ft prevented lysosomal membrane permeabilization (LMP), whereas Fe-Ft enhanced LMP. A 4-h pulse of Fe-Ft initially increased oxidative stress-mediated LMP that was reversed after another 3 h under standard culture conditions, suggesting that lysosomal iron is rapidly exported from lysosomes, with resulting upregulation of apo-ferritin that supposedly is autophagocytosed, thereby preventing LMP by binding intralysosomal redox-active iron. The obtained data suggest that upregulation of the stress protein ferritin is a rapid adaptive mechanism that counteracts LMP and ensuing apoptosis during oxidative stress. In addition, prolonged iron starvation was found to induce apoptotic cell death that, interestingly, was preceded by LMP, suggesting that LMP is a more general phenomenon in apoptosis than so far recognized. The findings provide new insights into aging and neurodegenerative diseases that are associated with enhanced amounts of cellular iron and show that lysosomal iron loading sensitizes to oxidative stress.
Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2011. Vol. 50, no 11, 1647-1658 p.
Apoptosis, Autophagy, Ferritin, Lysosomes, Oxidative stress, Redox-active iron, Free radicals
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-68690DOI: 10.1016/j.freeradbiomed.2011.03.014ISI: 000290603700021OAI: oai:DiVA.org:liu-68690DiVA: diva2:419710
Original Publication: Tino Kurz, Bertil Gustafsson and Ulf Brunk, Cell sensitivity to oxidative stress is influenced by ferritin autophagy, 2011, FREE RADICAL BIOLOGY AND MEDICINE, (50), 11, 1647-1658. http://dx.doi.org/10.1016/j.freeradbiomed.2011.03.014 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/2011-05-272011-05-272012-03-23