Protein degradation is a crucial cellular process in all‐living systems. Here, using Mycoplasma pneumoniae as a model organism, we defined the minimal protein degradation machinery required to maintain proteome homeostasis. Then, we conditionally depleted the two essential ATP‐dependent proteases. Whereas depletion of Lon results in increased protein aggregation and decreased heat tolerance, FtsH depletion induces cell membrane damage, suggesting a role in quality control of membrane proteins. An integrative comparative study combining shotgun proteomics and RNA‐seq revealed 62 and 34 candidate substrates, respectively. Cellular localization of substrates and epistasis studies supports separate functions for Lon and FtsH. Protein half‐life measurements also suggest a role for Lon‐modulated protein decay. Lon plays a key role in protein quality control, degrading misfolded proteins and those not assembled into functional complexes. We propose that regulating complex assembly and degradation of isolated proteins is a mechanism that coordinates important cellular processes like cell division. Finally, by considering the entire set of proteases and chaperones, we provide a fully integrated view of how a minimal cell regulates protein folding and degradation.

中文翻译：

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基因组减少生物肺炎支原体中的蛋白质质量控​​制和调节蛋白水解

蛋白质降解是全生命系统中一个关键的细胞过程。在这里，使用肺炎支原体作为模式生物，我们定义了维持蛋白质组稳态所需的最小蛋白质降解机制。然后，我们有条件地消耗了两种必需的 ATP 依赖性蛋白酶。Lon 的消耗会导致蛋白质聚集增加和耐热性降低，而 FtsH 消耗会导致细胞膜损伤，这表明它在膜蛋白的质量控制中起作用。一项结合鸟枪蛋白质组学和 RNA-seq 的综合比较研究分别揭示了 62 和 34 种候选底物。底物和上位性研究的细胞定位支持 Lon 和 FtsH 的独立功能。蛋白质半衰期测量也表明 Lon 调节的蛋白质衰变的作用。Lon 在蛋白质质量控​​制、降解错误折叠的蛋白质和未组装成功能复合物的蛋白质中起着关键作用。我们提出，调节分离蛋白质的复杂组装和降解是一种协调细胞分裂等重要细胞过程的机制。最后，通过考虑整套蛋白酶和分子伴侣，我们提供了一个关于最小细胞如何调节蛋白质折叠和降解的完全整合的视图。