Protein quality control and regulated proteolysis in the genome-reduced organism mycoplasma pneumoniae

Burgos, Raul; Weber, Marc; Martínez, Sira; Lluch-Senar, Maria 1982-; Serrano Pubull, Luis, 1982-

doi:http://dx.doi.org/10.15252/msb.20209530

Protein quality control and regulated proteolysis in the genome-reduced organism mycoplasma pneumoniae

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Burgos R, Weber M, Martínez S, Lluch-Senar M, Serrano L. Protein quality control and regulated proteolysis in the genome-reduced organism mycoplasma pneumoniae. Mol Syst Biol. 2020 Dec;16(12):e9530. DOI: 10.15252/msb.20209530

Abstract

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.