Nilsson E, Ghassemifar R, Brunk U T
Department of Pathology II, Faculty of Health Sciences, Linköping University, Sweden.
Histochem J. 1997 Nov-Dec;29(11-12):857-65. doi: 10.1023/a:1026441907803.
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.
关于溶酶体耐受性的普遍观点是，只要细胞仍然存活，这些细胞器通常相当稳定，因此不会因向细胞质中泄漏其众多强大的水解酶而诱导细胞损伤。我们认为这种观点基本上是错误的，并认为许多溶酶体相当脆弱，尤其是对氧化应激。此外，我们认为细胞变性，包括凋亡以及坏死，是溶酶体破坏之后的结果。我们发现溶酶体膜对氧化应激的稳定性不同，不仅在不同细胞类型之间存在差异，而且在同一类型的细胞之间以及单个细胞的溶酶体之间也存在差异。我们认为细胞对氧化应激的抗性主要取决于三个参数：（i）在过氧化氢到达并可能扩散到酸性液泡区室之前将其降解的能力；（ii）溶酶体膜对活性氧的抗性；以及（iii）溶酶体内具有氧化还原活性的低分子量铁的含量。如果铁催化的溶酶体内反应足够显著，就会导致溶酶体膜的过氧化和不稳定。由于过氧化氢降解酶的细胞合成、含铁金属蛋白的自噬降解程度、溶酶体在细胞质中的定位以及溶酶体内铁螯合的差异，上述三个参数在不同和相似细胞之间以及单个细胞的溶酶体之间也可能有所不同，这解释了它们在抗氧化应激抗性方面观察到的变异性。
