The ATP-dependent Lon protease is located in the mitochondrial matrix and oxidized proteins are among its primary targets for their degradation. Impairment of mitochondrial morphology and function together with apoptosis were observed in lung fibroblasts depleted for Lon expression while accumulation of carbonylated mitochondrial proteins has been reported for yeast and HeLa Lon deficient cells. In addition, age-related mitochondrial dysfunction has been associated with an impairment of Lon expression. Using a HeLa cell line stably transfected with an inducible shRNA directed against Lon, we have previously observed that Lon depletion results in a mild phenotype characterized by an increase of both production of reactive oxygen species and level of oxidized proteins (Bayot et al., 2014, Biochimie, 100: 38-47). In this study using the same cell line, we now show that Lon knockdown leads to modifications of the expression of a number of specific proteins involved in protein quality control, stress response and energy metabolism, as evidenced using a 2D gel-based proteomic approach, and to alteration of the mitochondrial network morphology. We also show that these effects are associated with decreased proliferation and can be modulated by culture conditions in galactose versus glucose containing medium.

中文翻译：

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线粒体Lon蛋白酶-耗尽的HeLa细胞显示出与蛋白质质量控​​制，应激反应和能量代谢有关的蛋白质组修饰。

ATP依赖的Lon蛋白酶位于线粒体基质中，氧化的蛋白质是其降解的主要目标之一。在缺失Lon表达的肺成纤维细胞中观察到线粒体形态和功能受损，同时凋亡，而据报道酵母和HeLa Lon缺陷细胞中羰基化线粒体蛋白蓄积。此外，年龄相关的线粒体功能障碍与Lon表达受损有关。使用稳定转染了针对Lon的可诱导shRNA的HeLa细胞系，我们之前已经观察到Lon耗竭会导致轻度表型，其特征在于活性氧的产生和氧化蛋白水平的增加（Bayot等人，2014 ，Biochimie，100：38-47）。在使用同一细胞系的这项研究中，我们现在证明Lon敲低会导致涉及蛋白质质量控​​制，应激反应和能量代谢的许多特定蛋白质的表达发生修饰，这已通过基于2D凝胶的蛋白质组学方法得到证明，并改变线粒体网络形态。我们还表明，这些作用与增殖减少有关，并且可以通过半乳糖与含葡萄糖的培养基中的培养条件进行调节。