liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Autophagy, ageing and apoptosis: The role of oxidative stress and lysosomal iron
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
2007 (English)In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, Vol. 462, no 2, 220-230 p.Article in journal (Refereed) Published
Abstract [en]

As an outcome of normal autophagic degradation of ferruginous materials, such as ferritin and mitochondrial metalloproteins, the lysosomal compartment is rich in labile iron and, therefore, sensitive to the mild oxidative stress that cells naturally experience because of their constant production of hydrogen peroxide. Diffusion of hydrogen peroxide into the lysosomes results in Fenton-type reactions with the formation of hydroxyl radicals and ensuing peroxidation of lysosomal contents with formation of lipofuscin that amasses in long-lived postmitotic cells. Lipofuscin is a non-degradable polymeric substance that forms at a rate that is inversely related to the average lifespan across species and is built up of aldehyde-linked protein residues. The normal accumulation of lipofuscin in lysosomes seems to reduce autophagic capacity of senescent postmitotic cells-probably because lipofuscin-loaded lysosomes continue to receive newly formed lysosomal enzymes, which results in lack of such enzymes for autophagy. The result is an insufficient and declining rate of autophagic turnover of worn-out and damaged cellular components that consequently accumulate in a way that upsets normal metabolism. In the event of a more substantial oxidative stress, enhanced formation of hydroxyl radicals within lysosomes jeopardizes the membrane stability of particularly iron-rich lysosomes, specifically of autophagolysosomes that have recently participated in the degradation of iron-rich materials. For some time, the rupture of a limited number of lysosomes has been recognized as an early upstream event in many cases of apoptosis, particularly oxidative stress-induced apoptosis, while necrosis results from a major lysosomal break. Consequently, the regulation of the lysosomal content of redox-active iron seems to be essential for the survival of cells both in the short- and the long-term. © 2007 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
2007. Vol. 462, no 2, 220-230 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-40899DOI: 10.1016/ ID: 54484OAI: diva2:261748
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2011-01-11

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Kurz, TinoTerman, AlexeiBrunk, Ulf
By organisation
Faculty of Health SciencesPharmacologyPathology
In the same journal
Archives of Biochemistry and Biophysics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 76 hits
ReferencesLink to record
Permanent link

Direct link