连接肺中蛋白酶体和线粒体的功能

Connecting the functions of the proteasome and mitochondria in the lung.

Keywords：MLE12 Mouse lung epithelial cells

关键词：MLE12 小鼠肺上皮细胞

哺乳动物：小鼠

组织：肺，腮
作者：Berschneider K
出版期刊：《Dissertation》（2016）

Abstract：

In living cells the cellular proteome is under constant remodeling as cells adapt to altered physiological states or as cellular proteins become misfolded and need to be degraded. The cellular processes which grant maintenance of a functional proteome are collectively called proteostasis. The proteasome constitutes one of the major intracellular protein degradation systems and is responsible for the turnover of damaged or unwanted proteins with almost 90% of the intracellular proteins being potential proteasome substrates. Especially for misfolded proteins, a timely degradation is necessary to avoid proteotoxic stress, e.g. by formation of protein aggregates. Degradation of proteins by the proteasome system is a very energy demanding process. Hence it was speculated that proteasomal function is interconnected with the function of mitochondria. Additionally, a correlation between mitochondrial and proteasomal dysfunction exists since a decline in the function of both systems is well recognized as hallmark of aging. However, it is unclear how proteasomal and mitochondrial function are directly linked together, especially in settings of chronic mitochondrial respiratory chain dysfunction. Moreover, limited knowledge is available to which extent proteasomal and mitochondrial functions contribute to aging processes specifically in lung tissue during healthy aging or in the development of age-related lung diseases such as chronic obstructive pulmonary disease.

文章摘要：

在活细胞中，当细胞适应改变的生理状态或细胞蛋白质错误折叠并需要降解时，细胞蛋白质组不断重塑。维持功能性蛋白质组的细胞过程统称为蛋白质稳态。蛋白酶体构成主要的细胞内蛋白质降解系统之一，并负责受损或不需要的蛋白质的周转，其中几乎 90% 的细胞内蛋白质是潜在的蛋白酶体底物。特别是对于错误折叠的蛋白质，需要及时降解以避免蛋白质毒性压力，例如通过形成蛋白质聚集体。蛋白酶体系统对蛋白质的降解是一个非常需要能量的过程。因此推测蛋白酶体功能与线粒体功能相互关联。此外，线粒体和蛋白酶体功能障碍之间存在相关性，因为这两个系统的功能下降被公认为衰老的标志。然而，尚不清楚蛋白酶体和线粒体功能如何直接联系在一起，尤其是在慢性线粒体呼吸链功能障碍的情况下。此外，在何种程度上蛋白酶体和线粒体功能在健康衰老过程中或在与年龄相关的肺部疾病（如慢性阻塞性肺病）的发展中特别是在肺组织中促进衰老过程的知识有限。

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文章题目、关键词与摘要译文仅用于参考。