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.
Highlights
Protein degradation is a key biological process that shapes the proteome of cells in response to internal and external signals
Genes encoding Map, Prp, Lon, and to a lesser extent peptide degradation such as MPN022 (Pip) and functions. These include MPN671 (FtsH) were induced by cold shock, suggesting that these proteases/peptidases could play a role in cold stress adaptation
Lon and PepA are encoded in operons regulated by the heat-shock transcription factor HrcA (MPN124), while Pip is in an operon with DnaJ (MPN021) that contains a degenerated motif for HrcA
Summary
Protein degradation is a key biological process that shapes the proteome of cells in response to internal and external signals. During stress conditions, misfolded and damaged proteins may accumulate in the cell with potential harmful consequences. In this scenario, chaperones and proteases play a key role as protein quality control factors assisting and reverting this situation through protein refolding or degradation (Mogk et al, 2011). Apart from maintaining protein homeostasis, protein degradation is an efficient mechanism to induce changes in cell physiology (Van Melderen & Aertsen, 2009). Protein degradation can potentially regulate many biological processes depending on the variety of proteases and the possible substrates existing in a cell system
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
