人成纤维细胞中的过氧化物酶体衰老
Peroxisome senescence in human fibroblasts.
作者信息
Legakis Julie E, Koepke Jay I, Jedeszko Chris, Barlaskar Ferdous, Terlecky Laura J, Edwards Holly J, Walton Paul A, Terlecky Stanley R
机构信息
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
出版信息
Mol Biol Cell. 2002 Dec;13(12):4243-55. doi: 10.1091/mbc.e02-06-0322.
Abstract
The molecular mechanisms of peroxisome biogenesis have begun to emerge; in contrast, relatively little is known about how the organelle functions as cells age. In this report, we characterize age-related changes in peroxisomes of human cells. We show that aging compromises peroxisomal targeting signal 1 (PTS1) protein import, affecting in particular the critical antioxidant enzyme catalase. The number and appearance of peroxisomes are altered in these cells, and the organelles accumulate the PTS1-import receptor, Pex5p, on their membranes. Concomitantly, cells produce increasing amounts of the toxic metabolite hydrogen peroxide, and we present evidence that this increased load of reactive oxygen species may further reduce peroxisomal protein import and exacerbate the effects of aging.
摘要
过氧化物酶体生物发生的分子机制已开始显现；相比之下，关于该细胞器在细胞衰老过程中的功能却知之甚少。在本报告中，我们描述了人类细胞过氧化物酶体与衰老相关的变化。我们发现衰老会损害过氧化物酶体靶向信号1（PTS1）蛋白的导入，尤其影响关键的抗氧化酶过氧化氢酶。这些细胞中过氧化物酶体的数量和外观发生了改变，并且这些细胞器在其膜上积累了PTS1导入受体Pex5p。与此同时，细胞产生的有毒代谢物过氧化氢的量不断增加，并且我们提供的证据表明，这种活性氧负荷的增加可能会进一步减少过氧化物酶体蛋白的导入，并加剧衰老的影响。
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