Lysosomal heterogeneity between and within cells with respect to resistance against oxidative stress |
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Authors: | Evalill Nilsson Reza Ghassemifar and Ulf T Brunk |
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Institution: | (1) Department of Pathology II, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden |
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Abstract: | The prevailing opinion on lysosomal endurance is that, as long as the cells are still alive, these organelles are generally
quite stable and, thus, do not induce cell damage by leaking their numerous powerful hydrolytic enzymes to the cytosol. We
suggest that this opinion is basically wrong and consider that many lysosomes are quite vulnerable, especially to oxidative
stress. Moreover, we suggest that cellular degeneration, including apoptosis as well as necrosis, follows upon lysosomal disruption.
We have found differing stability of lysosomal membranes to oxidative stress, not only among different cell types, but also
between cells of the same type and between lysosomes of individual cells. We suggest that cellular resistance to oxidative
stress is mainly a function of three parameters: (i) the capacity to degrade hydrogen peroxide before it reaches, and may
diffuse into, the acidic vacuolar compartment; (ii) the resistance to reactive oxygen species of lysosomal membranes; and
(iii) the intralysosomal amounts of redox-active, low molecular weight iron. Iron-catalysed intralysosomal reactions, if pronounced
enough, result in peroxidation and destabilization of the lysosomal membrane. Owing to differences in the cellular synthesis
of hydrogen peroxide-degrading enzymes, degree of autophagocytotic degradation of iron-containing metalloproteins, lysosomal
localization within the cytoplasm and intralysosomal iron chelation, the above three parameters may vary between both different
and similar cells and between lysosomes of individual cells as well, explaining their observed variability with respect to
resistance against oxidative stress
This revised version was published online in November 2006 with corrections to the Cover Date. |
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